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1.
Increased bone resorption mediated by osteoclasts causes various diseases such as osteoporosis and bone erosion in rheumatoid
arthritis (RA). Osteoclasts are derived from the monocyte/macrophage lineage, but the precise origin remains unclear. In the
present study, we show that the purified CD16- human peripheral blood monocyte subset, but not the CD16+ monocyte subset, differentiates into osteoclast by stimulation with receptor activator of NF-κB ligand (RANKL) in combination
with macrophage colony-stimulating factor (M-CSF). Integrin-β3 mRNA and the integrin-αvβ3 heterodimer were only expressed
on CD16- monocytes, when they were stimulated with RANKL + M-CSF. Downregulation of β3-subunit expression by small interfering RNA
targeting β3 abrogated osteoclastogenesis from the CD16- monocyte subset. In contrast, the CD16+ monocyte subset expressed larger amounts of tumor necrosis factor alpha and IL-6 than the CD16- subset, which was further enhanced by RANKL stimulation. Examination of RA synovial tissue showed accumulation of both CD16+ and CD16- macrophages. Our results suggest that peripheral blood monocytes consist of two functionally heterogeneous subsets with distinct
responses to RANKL. Osteoclasts seem to originate from CD16- monocytes, and integrin β3 is necessary for osteoclastogenesis. Blockade of accumulation and activation of CD16- monocytes could therefore be a beneficial approach as an anti-bone resorptive therapy, especially for RA. 相似文献
2.
Timothy L. Frankel William Burns John Riley Richard A. Morgan Jeremy L. Davis Kenichi Hanada Martha Quezado Steven A. Rosenberg Richard E. Royal 《Cancer immunology, immunotherapy : CII》2010,59(12):1757-1769
In a recent clinical trial, a patient exhibited regression of several pancreatic cancer metastases following the administration
of the immune modulator Ipilimumab (anti-CTLA-4 antibody). We sought to characterize the immune cells responsible for this
regression. Tumor infiltrating lymphocytes (TIL-2742) and an autologous tumor line (TC-2742) were expanded from a regressing
metastatic lesion excised from this patient. Natural killer (NK) cells predominated in the TIL (92% CD56+) with few T cells (12% CD3+). A majority (88%) of the NK cells were CD56brightCD16−. TIL-2742 secreted IFN-γ and GM-CSF following co-culture with TC-2742 and major histocompatibility complex mismatched pancreatic
tumor lines. After sorting TIL-2742, the purified CD56+CD16−CD3− subset showed reactivity similar to TIL-2742 while the CD56−CD16−CD3+ cells exhibited no tumor recognition. In co-culture assays, TIL-2742 and the NK subset expressed high reactivity to several
pancreatic and prostate cancer cell lines and could lyse the autologous tumor as well as pancreas and prostate cancer lines.
Reactivity was partially abrogated by blockade of TRAIL. We thus identified a unique subset of NK cells (CD56brightCD16dim) isolated from a regressing metastatic pancreatic cancer in a patient responding to Ipilimumab. This represents the first
report of CD56+CD16− NK cells with apparent specificity for pancreatic and prostate cancer cell lines and associated with tumor regression following
the treatment with an immune modulating agent. 相似文献
3.
Acute coronary syndrome (ACS) is a group of clinical symptoms that results from complete or partial occlusive thrombus, which
is caused by coronary an atherosclerotic plaque rupture or erosion. According to a recent study, CD4+ CD28− T cells are found in atherosclerotic plaques and the peripheral circulation blood in patients with ACS, these cells play
an important role in plaque ruptures. CD4+ CD28− T cells are an unusual subset of helper cells, which expand and have harmful effects in ACS. In this review, we discuss the
current issues on the generation of CD4+ CD28− T cells and focus on their phenotypic and functional characteristics relevant to the development of cardiovascular events.
Targeting the CD4+ CD28− T cells subset in ACS could provide novel therapeutic means to prevent acute life-threatening coronary events. 相似文献
4.
Based on the difference in the CD14 and CD16 expression, two subsets of monocytes were identified in human and other mammalian
blood. These subsets have different patterns of adhesion molecules and chemokine receptors that suggests the different mode
of their interaction with endothelium and tissue traffic. Here, we investigated the ability of CD14+CD16+ and CD14++CD16− monocytes to adhere to endothelial cell monolayer in presence or absence of pro- and anti-inflammatory cytokines. We demonstrated
that CD14+CD16+ monocytes had a higher level of adhesion to intact monolayer of endothelial cells than CD14++CD16− monocytes. Adhesion of CD14++CD16− and CD14+CD16+ monocytes significantly increased in the presence of TNFα or its combination with other cytokines. IFNγ and IL-4 alone did
not affect the adhesion of monocytes. These results show that CD14++CD16− and CD14+CD16+ monocytes can be recruited to the inflamed endothelium, but CD14+CD16+ monocytes adhere to endothelial cells without inflammations twice as strongly as CD14++CD16− monocytes. 相似文献
5.
Flacher V Sparber F Tripp CH Romani N Stoitzner P 《Cancer immunology, immunotherapy : CII》2009,58(7):1137-1147
Langerhans cells, a subset of skin dendritic cells in the epidermis, survey peripheral tissue for invading pathogens. In recent
functional studies it was proven that Langerhans cells can present exogenous antigen not merely on major histocompatibility
complexes (MHC)-class II molecules to CD4+ T cells, but also on MHC-class I molecules to CD8+ T cells. Immune responses against topically applied antigen could be measured in skin-draining lymph nodes. Skin barrier
disruption or co-application of adjuvants was required for maximal induction of T cell responses. Cytotoxic T cells induced
by topically applied antigen inhibited tumor growth in vivo, thus underlining the potential of Langerhans cells for immunotherapy.
Here we review recent work and report novel observations relating to the potential use of Langerhans cells for immunotherapy.
We investigated the potential of epicutaneous immunization strategies in which resident skin dendritic cells are loaded with
tumor antigen in situ. This contrasts with current clinical approaches, where dendritic cells generated from progenitors in
blood are loaded with tumor antigen ex vivo before injection into cancer patients. In the current study, we applied either
fluorescently labeled protein antigen or targeting antibodies against DEC-205/CD205 and langerin/CD207 topically onto barrier-disrupted
skin and examined antigen capture and transport by Langerhans cells. Protein antigen could be detected in Langerhans cells
in situ, and they were the main skin dendritic cell subset transporting antigen during emigration from skin explants. Potent
in vivo proliferative responses of CD4+ and CD8+ T cells were measured after epicutaneous immunization with low amounts of protein antigen. Targeting antibodies were mainly
transported by langerin+ migratory dendritic cells of which the majority represented migratory Langerhans cells and a smaller subset the new langerin+ dermal dendritic cell population located in the upper dermis. The preferential capture of topically applied antigen by Langerhans
cells and their ability to induce potent CD4+ and CD8+ T cell responses emphasizes their potential for epicutaneous immunization strategies.
This article is a symposium paper from the conference “Immunotherapy—From Basic Research to Clinical Applications,” Symposium
of the Collaborative Research Center (SFB) 685, held in Tübingen, Germany, 6–7 March 2008. 相似文献
6.
Gordana Konjević Katarina Mirjačić Martinović Ana Vuletić Vladimir Jurisić Ivan Spužić 《The Journal of membrane biology》2009,230(3):113-123
The aim of this study was to estimate the distribution and density of a representative set of activating and inhibitory receptors
on gated natural killer (NK) cells, as well as on their bright and dim subsets, and to correlate the receptor expression with
NK cell activity for healthy individuals on CD3−CD16+ NK cells. We show that in 43 healthy controls NK cell activity against K562 target cells was 37.34% (E:T, 80:1) by standard
chromium release assay. The expression of receptors on NK cells and their subsets was analyzed by flow cytometry. The cytotoxic
CD3−CD16bright NK subset constituted 78.97%, while the regulatory CD3−CD16dim NK subset constituted 21.03% of NK cells. We show the distribution of NKG2D, CD161, CD158a, and CD158b receptors on CD3−CD16+ NK cells in peripheral blood lymphocytes (PBLs), on gated NK cells, and on the CD3−CD16bright and CD3−CD16dim subsets. Contrary to CD158a and CD158b killer immunoglobulin-like receptors (KIRs), there is a significant positive correlation
of NKG2D and CD161 expression with NK cytotoxicity. We show the kinetics of change in CD3−CD16+NK/K562 conjugate composition, together with the stronger target binding capacity of CD16bright NK cells. Furthermore, we show that after coculture of PBLs with K562 the expression of CD107a, a degranulation marker, on
CD3−CD16+NK cells and subsets is time dependent and significantly higher on the cytotoxic CD3−CD16bright NK subset. The novel data obtained regarding expression of NK cell activating and inhibitory receptors for healthy individuals
may aid in detecting changes that are associated with various diseases. 相似文献
7.
C. A. Savary Monica L. Grazziutti Bohuslav Melichar Donna Przepiorka Ralph S. Freedman Richard E. Cowart D. M. Cohen E. J. Anaissie Darren G. Woodside Bradley W. McIntyre Duane L. Pierson Neal R. Pellis John H. Rex 《Cancer immunology, immunotherapy : CII》1997,45(5):234-240
We studied the potential of multidimensional flow cytometry to evaluate the frequency and maturation/activation status of
dendritic cells in minimally manipulated peripheral blood mononuclear cell preparations (i.e., only separated on Ficoll-Hypaque)
of normal donors and cancer patients. A rare subset of HLA-DR+ leukocytes (less than 1% mononuclear cells) was detected in blood of normal donors that displayed all the features of dendritic
cells: these cells had high forward-light-scatter characteristics and coexpressed CD4, CD86 and CD54 surface antigens, but
lacked the lineage-associated surface markers of T cells, B cells, monocytes, granulocytes or NK i.e. they were CD3–, CD19–, CD20–, CD14–, CD11b–, CD16–, CD56–). These physical and phenotypic properties were virtually identical to those of immunomagnetically sorted leukocytes characterized
as dendritic-cells on the basis of morphology, phenotype and high stimulatory activity in allogeneic mixed-lymphocyte cultures.
Using this flow-cytometric approach we observed that the frequency of dendritic cell-like cells in peripheral blood mononuclear
cell specimens of cancer patients receiving chemotherapy alone or those recovering from stem cell transplantation was significantly
lower than that of normal individuals (mean ± SE: 0.36 ± 0.05%, 0.14 ± 0.06%, and 0.75 ± 0.04% respectively). Multidimensional
flow-cytometric analysis of dendritic cells might represent an important new tool for assessing immunocompetence, and for
monitoring the effects of therapeutic regimens on the immune system.
Received: 20 June 1997 / Accepted: 14 August 1997 相似文献
8.
Mundy-Bosse BL Young GS Bauer T Binkley E Bloomston M Bill MA Bekaii-Saab T Carson WE Lesinski GB 《Cancer immunology, immunotherapy : CII》2011,60(9):1269-1279
Interferon-alpha (IFN-α) promotes anti-tumor immunity through its actions on immune cells. We hypothesized that elevated percentages
of myeloid-derived suppressor cells (MDSC) and increased pro-inflammatory cytokines in peripheral blood would be associated
with impaired response to IFN-α in patients with gastrointestinal (GI) malignancies. This study evaluated relationships between
plasma IL-6, IL-10, circulating MDSC subsets, and IFN-α-induced signal transduction in 40 patients with GI malignancies. Plasma
IL-6 and IL-10 were significantly higher in patients versus normal donors. CD33+HLADR−CD11b+CD15+ and CD33+HLADR−/lowCD14+ MDSC subsets were also elevated in patients versus normal donors (P < 0.0001). Plasma IL-6 was correlated with CD33+HLADR−CD15+ MDSC (P = 0.008) and IL-10 with CD33+HLADR−CD15− MDSC (P = 0.002). The percentage of CD15+ and CD15− but not CD14+ MDSC subsets were inversely correlated with IFN-α-induced STAT1 phosphorylation in CD4+ T cells, while co-culture with in vitro generated MDSC led to reduced IFN-α responsiveness in both PBMC and the CD4+ subset of T cells from normal donors. Exploratory multivariable Cox proportional hazards models revealed that an increased
percentage of the CD33+HLADR−CD15− MDSC subset was associated with reduced overall survival (P = 0.049), while an increased percentage of the CD33+HLADR−/lowCD14+ subset was associated with greater overall survival (P = 0.033). These data provide evidence for a unique relationship between specific cytokines, MDSC subsets, and IFN-α responsiveness
in patients with GI malignancies. 相似文献
9.
Pascale Hubert Roland Greimers Elizabeth Franzen-Detrooz Jean Doyen Pierre Delanaye Jacques Boniver Philippe Delvenne 《Cancer immunology, immunotherapy : CII》1998,47(2):81-89
Dendritic cells (DC) are the most efficient antigen presenting cells. The clinical use of DC as vectors for antitumor and
anti-infectious disease immunotherapy has been limited by their low level and accessibility in normal tissue. Substantial
numbers of DC can be generated from peripheral blood cultured in the presence of interleukin-4 (IL-4) and granulocyte/macrophage-colony-stimulating
factor (GM-CSF). We showed in this study that substantial numbers of DC can be obtained from the peripheral blood of patients
with (pre)neoplastic lesions of the uterine cervix. The procedure required relatively small blood samples (10 ml) and the
presence of 100 U/ml IL-4 and 800 U/ml GM-CSF in the culture medium. There was no significant difference in the morphology,
yield, phenotype and function of generated DC between patients with cervical (pre)neoplastic lesions and healthy individuals.
When the hematopoietic factor Flt3 ligand (Flt3L, 40 ng/ml) was added, there was an average increase in the DC population
of 26% compared to cultures with GM-CSF and IL-4 alone. Approximately 1.2 × 106 cells with the characteristics of dendritic cells could be obtained when Flt3L was included in the medium. The addition of
Flt3L did not modify the phenotypic profile of DC (HLA-DR+, CD1a+, CD4+, CD54+, CD80+, CD86+, CD40+, CD3− and CD14−). In addition, Flt3L generated functional DC capable of stimulating the proliferation of alloreactive T cells. These results
suggest that Flt3L, in association with GM-CSF and IL-4, provides an advantageous tool for the large-scale generation of DC
and that an immunotherapy based on the use of DC generated in vitro is possible in patients with (pre)neoplastic lesions of
the uterine cervix.
Received: 8 January 1998 / Accepted: 30 April 1998 相似文献
10.
Kida Y Tsuji-Kawahara S Ostapenko V Kinoshita S Kajiwara E Kawabata H Yuasa T Nishide I Yukawa S Ichinose M Miyazawa M 《Cancer immunology, immunotherapy : CII》2006,55(12):1459-1469
Hyperthermia (HT), in combination with other conventional therapeutic modalities, has become a promising approach in cancer therapy. In addition to heat-induced apoptosis, an augmented immunological effect is considered to be a benefit of hyperthermic treatment over chemo- or radiotherapy. Here, we investigated the effect of regional HT targeting the liver on immune cells, especially T cells and antigen-presenting cells, which are important in recognizing and eliminating tumor cells and pathogens such as viruses. In healthy volunteers exposed to such regional HT, both CD4+ and CD8+ T cells that express an activation marker CD69 increased transiently at 1 h post-treatment, with a subsequent decrease to base levels at 6 h after the treatment. At 24 h post-treatment, the percentage of CD69-positive cells significantly increased again but only among CD8+ T cells. IFN-γ production from PHA-stimulated peripheral blood mononuclear cells was gradually and significantly increased in the 2 days following the heating procedure, peaking at 36 h post-treatment. Furthermore, we found marked increases in plasma levels of IL-1β and IL-6 starting at 24 h post-treatment. With regard to the number of each leukocyte subpopulation, a transient and dramatic decrease in the number of a subset of monocytes, CD14+ CD16− cells, was observed at 1 h after the hyperthermic treatment, suggesting that the regional HT aimed at the liver may have influenced the extravasation of blood monocytes. No significant changes in T-cell activities or monocyte counts were observed in the volunteers exposed to heating of the lungs or the legs. These results suggest that heating of the liver may efficiently induce cellular immune responses to liver cancers. 相似文献
11.
The presence of a relatively mature CD4+ CD8− (SP) T cell subset in mouse thymus has been demonstrated. Composing of 10% of total CD4SP thymocytes, this subset is defined
by the absence of 3G11 and 6C10 expression with a phenotype of CD69+/−, HSAmed/lo and heterogeneous for Qa-2 expression. The proliferation capability of TCRαβ+ 3Gl l− 6C10− CD4+ CD8− thymocytes was high while using Con A stimulus. And Con A stimulation could result in secretion of IL4, IL-10, IL-6 and a
little amount of IFNγ. IL-2 was barely detectable. This is distinct from typical Th0 type cytokines. The cells of this subset
were NK1.1 negative, but strongly expressed GATA-3 mRNA. The results suggest that the CD4+ subset of 3G11− 6C10− NK1.1− phenotype possesses immunocompetent cells with functions characteristic of Th2-like cytokines, which may indicate the cells
at transitional status from Th0 to Th2, with a propensity to Th2.
Project supported by the National Natural Science Foundation of China (Grant No. 39730410). 相似文献
12.
The presence of a relatively mature CD4+ CD8− (SP) T cell subset in mouse thymus has been demonstrated. Composing of 10% of total CD4SP thymocytes, this subset is defined by the absence of 3G11 and 6C10 expression with a phenotype of CD69+/−, HSAmed/lo and heterogeneous for Qa-2 expression. The proliferation capability of TCRαβ+ 3Gl l− 6C10− CD4+ CD8− thymocytes was high while using Con A stimulus. And Con A stimulation could result in secretion of IL4, IL-10, IL-6 and a little amount of IFNγ. IL-2 was barely detectable. This is distinct from typical Th0 type cytokines. The cells of this subset were NK1.1 negative, but strongly expressed GATA-3 mRNA. The results suggest that the CD4+ subset of 3G11− 6C10− NK1.1− phenotype possesses immunocompetent cells with functions characteristic of Th2-like cytokines, which may indicate the cells at transitional status from Th0 to Th2, with a propensity to Th2. 相似文献
13.
Jennifer A. Manuzak Stephanie M. Dillon Eric J. Lee Zachary M. Dong Daniel K. Hecht Cara C. Wilson 《Journal of virology》2013,87(24):13252-13262
The level of microbial translocation from the intestine is increased in HIV-1 infection. Proinflammatory cytokine production by peripheral antigen-presenting cells in response to translocated microbes or microbial products may contribute to systemic immune activation, a hallmark of HIV-1 infection. We investigated the cytokine responses of peripheral blood myeloid dendritic cells (mDCs) and monocytes to in vitro stimulation with commensal enteric Escherichia coli in peripheral blood mononuclear cells (PBMC) from untreated HIV-1-infected subjects and from uninfected controls. Levels of interleukin 23 (IL-23) produced by PBMC from HIV-1-infected subjects in response to E. coli stimulation were significantly higher than those produced by PBMC from uninfected subjects. IL-23 was produced primarily by CD16+ monocytes. This subset of monocytes was increased in frequency and expressed higher levels of Toll-like receptor 4 (TLR4) in HIV-1-infected individuals than in controls. Blocking TLR4 on total CD14+ monocytes reduced IL-23 production in response to E. coli stimulation. Levels of soluble CD27, an indicator of systemic immune activation, were elevated in HIV-1-infected subjects and were associated with the percentage of CD16+ monocytes and the induction of IL-23 by E. coli, providing a link between these parameters and systemic inflammation. Taken together, these results suggest that IL-23 produced by CD16+ monocytes in response to microbial stimulation may contribute to systemic immune activation in HIV-1-infected individuals. 相似文献
14.
Garibaldi S Barisione C Ghigliotti G Spallarossa P Barsotti A Fabbi P Corsiglia L Palmieri D Palombo D Brunelli C 《Molecular biology reports》2012,39(6):6745-6752
The cell adhesion molecule CD146 is normally located at the endothelial cell-to-cell junction and colocalizes with actin cytoskeleton.
The soluble form of CD146 (sCD146) has been identified in the endothelial cell supernatant and in normal human plasma, and
is increased in pathologic conditions with altered endothelial function. Soluble CD146 binding to monocytes promotes their
transendothelial migration, which represents a central step in the development of atherosclerotic plaque. Since peripheral
blood monocytes are characterized by a phenotypic and functional heterogeneity, with different transendothelial migration
capacity, we hypothesized that monocyte subsets differently bind sCD146. Based on surface CD14 and CD16 expression monocytes
were distinguished by flow cytometry (FACS) into three subsets: CD14++/CD16−, CD14++/CD16+ and CD14+/CD16+. CD16+ monocytes
have been found to possess higher transendothelial migration ability. FACS analysis on blood monocytes from 30 healthy subjects
revealed that higher percentages of CD14++/CD16+ (median, first and third quartile: 2.26, 1.62–3.87) and of CD14+/CD16+ (2.59,
1.28–4.80) were positive for CD146 (both p < 0.01), in comparison to CD14++/CD16− (0.66, 0.47–1.01). Moreover, in vitro treatment of ficoll separated monocytes with
recombinant CD146 showed that both CD16+ subsets increased their percentage of CD146-positive events compared to CD16− monocytes
(p < 0.01). Soluble CD146 levels were evaluated by ELISA in plasma samples of subjects from our study group and showed a correlation
with percentage of CD146-positive CD14+/CD16+ monocyte subset. In this work we have demonstrated that monocyte subsets behave
differently with regard to their sCD146 binding activity; because binding of CD146 influences transendothelial migration of
monocytes, modulation of monocyte-CD146 interaction may represent a potential target to limit atherosclerotic plaque development. 相似文献
15.
Bo Ruem Yoon Su-Jin Yoo Yeon ho Choi Yeon-Ho Chung Jinhyun Kim In Seol Yoo Seong Wook Kang Won-Woo Lee 《PloS one》2014,9(10)
Monocytes function as crucial innate effectors in the pathogenesis of chronic inflammatory diseases, including autoimmunity, as well as in the inflammatory response against infectious pathogens. Human monocytes are heterogeneous and can be classified into three distinct subsets based on CD14 and CD16 expression. Although accumulating evidence suggests distinct functions of monocyte subsets in inflammatory conditions, their pathogenic roles in autoimmune diseases remain unclear. Thus, we investigated the phenotypic and functional characteristics of monocytes derived from synovial fluid and peripheral blood in RA patients in order to explore the pathogenic roles of these cells. In RA patients, CD14+CD16+, but not CD14dimCD16+, monocytes are predominantly expanded in synovial fluid and, to a lesser degree, in peripheral blood. Expression of co-signaling molecules of the B7 family, specifically CD80 and CD276, was markedly elevated on synovial monocytes, while peripheral monocytes of RA and healthy controls did not express these molecules without stimulation. To explore how synovial monocytes might gain these unique properties in the inflammatory milieu of the synovial fluid, peripheral monocytes were exposed to various stimuli. CD16 expression on CD14+ monocytes was clearly induced by TGF-β, although co-treatment with IL-1β, TNF-α, or IL-6 did not result in any additive effects. In contrast, TLR stimulation with LPS or zymosan significantly downregulated CD16 expression such that the CD14+CD16+ monocyte subset could not be identified. Furthermore, treatment of monocytes with IFN-γ resulted in the induction of CD80 and HLA-DR expression even in the presence of TGF-β. An in vitro assay clearly showed that synovial monocytes possess the unique capability to promote Th1 as well as Th17 responses of autologous peripheral CD4 memory T cells. Our findings suggest that the cytokine milieu of the synovial fluid shapes the unique features of synovial monocytes as well as their cardinal role in shaping inflammatory T-cell responses in RA. 相似文献
16.
Interrelation of lymphocyte subpopulations in peripheral blood under cervical papillomavirus infection 总被引:1,自引:0,他引:1
Spivak MYa Lakatosh VP Lazarenko LM Lyanenko LM Azarskova MV Mikhailenko OM Tkáciková L Boroda AM 《Folia microbiologica》1999,44(6):721-725
T(CD3+)-, B(CD19+)-lymphocytes and their subsets (CD4+, CD8+, CD3+, DR+, CD3− DR+) in peripheral blood of patients with CIN I, CIN II, CIN III and cancerin situ associated with HPV infection were evaluated. In peripheral blood of women with CIN II, CIN III and cancerin situ the number of T-lymphocytes which expressed CD3+ DR+ antigen decreased. In patients with CIN I, CIN III and cancerin situ the level of the CD4+ cells decreased; the level of the CD8+ cells increased. These patients had a lower CD4/CD8 ratio, the number of B cells being standard. The results may have important
implications in the prognosis and immunotherapy of HPV infection.
Presented at theInternational Conference on Recent Problems in Microbiology and Immunology, Košice (Slovakia), 13–15 October 1999. 相似文献
17.
Jamal Hussen Anna Düvel Olivier Sandra David Smith Iain Martin Sheldon Peter Zieger Hans-Joachim Schuberth 《PloS one》2013,8(8)
Murine and human peripheral blood monocytes are heterogeneous in size, granularity, nuclear morphology, phenotype and function. Whether and how bovine blood monocytes follow this pattern was analyzed in this study. Flow cytometrically, classical monocytes (cM) CD14+ CD16−, intermediate monocytes (intM) CD14+ CD16+ and nonclassical monocytes (ncM) CD14+ CD16+ were identified, with cM being the predominant subset (89%). cM showed a significant lower expression of CD172a, intM expressed the highest level of MHC class II molecules, and ncM were low positive for CD163. Compared to cM and intM, ncM showed a significantly reduced phagocytosis capacity, a significantly reduced generation of reactive oxygen species, and reduced mRNA expression of CXCL8, CXCL1 and IL-1β after LPS stimulation. Based on IL-1β secretion after LPS/ATP stimulation, the inflammasome could be activated in cM and intM, but not in ncM. IFNγ increased the expression of CD16 selectively on cM and induced a shift from cM into intM in vitro. In summary, bovine CD172a-positive mononuclear cells define three monocyte subsets with distinct phenotypic and functional differences. Bovine cM and intM share homologies with their human counterparts, whereas bovine ncM are not inflammatory monocytes. 相似文献
18.
Synergy between interleukin-2 and prothymosin α for the increased generation of cytotoxic T lymphocytes against autologous human carcinomas 总被引:3,自引:0,他引:3
Voutsas IF Baxevanis CN Gritzapis AD Missitzis I Stathopoulos GP Archodakis G Banis C Voelter W Papamichail M 《Cancer immunology, immunotherapy : CII》2000,49(8):449-458
Peripheral blood mononuclear cells (PBMC) from cancer patients were cultured in vitro with irradiated autologous tumor cells
isolated from malignant effusions (mixed lymphocyte tumor cultures, MLTC) and low-dose (50 IU/ml) recombinant interleukin-2
(IL-2). The combination of IL-2 and prothymosin α (ProTα) resulted in a greater PBMC-induced response to the autologous tumor
than that brought about by IL-2 alone. In particular, ProTα specifically enhanced the CD4+ T-cell-mediated proliferation against the autologous tumor. CD4+ T cells seemed to recognize tumor antigens presented by HLA-DR molecules expressed on the autologous monocytes, since preincubation
of the latter with an anti-HLA-DR monoclonal antibody (mAb) abrogated the response. In addition, MLTC set up with IL-2 and
ProTα also generated more MHC-class-I-restricted cytotoxic T lymphocytes (CTL) against the autologous tumor than did MLTC
set up with IL-2 alone. The MLTC-induced CTL contained high levels of cytoplasmic perforin and their development was strictly
dependent on the presence of both autologous CD4+ T cells and monocytes. In the absence of either population there was a strong impairment of both proliferative and cytotoxic
responses which was not restored by the presence of ProTα. In contrast, when both cell populations were present, ProTα exerted
optimal enhancement of CD4+ T cell proliferation, which was associated with potentiated CTL responses. Our data emphasize the role of ProTα for the enhancement
of IL-2-induced CTL responses against autologous tumor cells. Such responses require collaborative interactions between CD4+, CD8+ T cells and monocytes as antigen-presenting cells. Our data are relevant for adoptive immunotherapeutic settings utilizing
IL-2 and ProTα-induced autologous-tumor-specific CTL.
Received: 2 March 2000 / Accepted: 1 June 2000 相似文献
19.
Griffiths RW Elkord E Gilham DE Ramani V Clarke N Stern PL Hawkins RE 《Cancer immunology, immunotherapy : CII》2007,56(11):1743-1753
Background Regulatory T cells are important in maintaining immune homeostasis, mediating peripheral tolerance and preventing autoimmunity.
Increased frequencies of CD4+CD25high T regulatory (TReg) cells have been documented in the peripheral blood of patients with several types of cancer consistent with a role in tumour
escape from immunological control. We have investigated the presence of TReg cells systemically and in situ in previously untreated patients with renal cell carcinoma (RCC).
Results We have shown that there is a significant increased frequency of CD4+CD25high T cells in RCC patients (n = 49) compared to normal donors (n = 38), respectively, 2.47% versus 1.50%; P < 0.0001. We confirmed these data using the FOXP3 marker of TReg cells in a subset of these patients and normal donors. The population of TReg cells identified showed the expected phenotype with CD4+CD25high population in both RCC patients and normal donors contained higher proportions of CD45RO and GITR than CD4+CD25−/low populations and exhibiting suppressive activity in an anti-CD3 and anti-CD28 induced proliferation assay. CD4+FOXP3+ T cells were detected in the tumour microenvironment by immunofluorescence and the numbers enumerated in lymphocytes recovered
following enzymatic disaggregations of biopsies; their frequency was higher in the tumour than the peripheral blood of the
same patients. The early follow up data show an association between higher peripheral blood regulatory T-cell count and adverse
overall survival.
Conclusion These data confirm the increase of TReg cells in RCC patients and provide impetus to further investigate modulation of TReg activity in RCC patients as part of therapy.
Richard W. Griffiths and Eyad Elkord have equally contributed to the study. 相似文献
20.
Expansion and characteristics of human T regulatory type 1 cells in co-cultures simulating tumor microenvironment 总被引:1,自引:0,他引:1
Bergmann C Strauss L Zeidler R Lang S Whiteside TL 《Cancer immunology, immunotherapy : CII》2007,56(9):1429-1442
Objective Chronic inflammation and cancer development are associated with dysregulated immune responses and the presence of regulatory
T cells (Treg). To study the role of Treg in tumor cell escape from immune surveillance, an in vitro model simulating the tumor microenvironment and promoting the
induction and expansion of IL-10+ Treg type 1 (Tr1) was established.
Methods An in vitro co-culture system (IVA) included an irradiated head and neck squamous cell carcinoma cell line, immature dendritic
cells (iDC), CD4+CD25− T cells and cytokines, IL-2 (10 IU/ml), IL-10 (20 IU/ml), IL-15 (20 IU/ml) ± 1 nM rapamycin. Autologous iDC and CD4+CD25− T cells were obtained from the peripheral blood of 15 normal donors. Co-cultures were expanded for 10 days. Proliferating
lymphocytes were phenotyped by multi-color flow cytometry. Their suppressor function was measured in CFSE inhibition assays ± neutralizing
anti-IL-10 mAb and using transwell cultures. Culture supernatants were tested for IL-4, IL-10, TGF-β and IFN-γ in ELISA.
Results In the IVA, low doses of IL-2, IL-10 and IL-15 promoted induction and expansion of CD3+CD4+CD25−IL2Rβ+IL2Rγ+FoxP3+CTLA-4+IL-10+ cells with suppressor activity (mean suppression ± SD = 58 ± 12%). These suppressor cells produced IL-10 (mean ± SD = 535 ± 12 pg/ml)
and TGF-β (mean ± SD = 512 ± 38 pg/ml), but no IL-4 or IFN-γ. Suppressor function of co-cultures correlated with the percent
of expanding IL-10+ Tr1 cells (r
2 = 0.9; P < 0.001). The addition of rapamycin enriched Tr1 cells in all co-cultures. Neutralizing anti-IL-10 mAb abolished suppressive
activity. Suppression was cell-contact independent.
Conclusion The tumor microenvironment promotes generation of Tr1 cells which have the phenotype distinct from that of CD4+CD25highFoxP3+ nTreg and mediate IL-10 dependent immune suppression in a cell-contact independent manner. Tr1 cells may play a critical
role in cancer progression. 相似文献