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1.
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
2.
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
3.
4.
Bone marrow-derived cells have been postulated as a source of multipotent mesenchymal stem cells (MSC). However, the whole
fraction of MSC remains heterogeneous and the expansion of primitive subset of these cells is still not well established.
Here, we optimized the protocol for propagating the low-adherent subfraction of MSC which results in long-term expansion of
population characterized by CD45−CD14+CD34+ phenotype along with expression of common MSC markers. We established that the expanded MSC are capable of differentiating
into endothelial cells highly expressing angiogenic markers and exhibiting functional properties of endothelium. Moreover,
we found these cells to be multipotent and capable of giving rise into cells from neuronal lineages. Interestingly, the expanded
MSC form characteristic cellular spheres in vitro indicating primitive features of these cells. In sum, we isolated the novel multipotent subpopulation of CD45−CD14+ CD34+ bone marrow-derived cells that could be maintained in long-term culture without losing this potential. 相似文献
5.
V. E. Yurinskaya T. S. Goryachaya A. A. Rubashkin A. V. Shirokova A. A. Vereninov 《Cell and Tissue Biology》2010,4(5):457-463
The K+, Na+, and Cl− balance and K+ (Rb+) and 36Cl− fluxes in U937 cells induced to apoptosis by 0.2 or 1 μM staurosporine were studied using flame emission and radioisotope
techniques. It is found that two-thirds of the total decrease in the amount of intracellular osmolytes in apoptotic cells
is accounted for by monovalent ions and one-third consists of other intracellular osmolytes. A decrease in the amount of monovalent
ions results from a decrease in the amount of K+ and Cl− and an increase in the Na+ content. The rate of 36Cl−, Rb+ (K+), and 22Na+ equilibration between cells and the medium was found to significantly exceed the rate of apoptotic change in the cellular
ion content, which indicates that unidirectional influxes and effluxes during apoptosis may be considered as being in near
balance. The drift of the ion flux balance in apoptosis caused by 0.2 μM staurosporine was found to be associated with the
increased ouabain-resistant Rb+ (K+) channel influx and insignificantly altered the ouabain-sensitive pump influx. Severe apoptosis induced by 1 μM staurosporine
is associated with reduced pump fluxes and slightly changed channel Rb+ (K+) fluxes. In apoptotic cells, the 1.4–1.8-fold decreased Cl− level is accompanied by a 1.2–1.6-fold decreased flux. 相似文献
6.
Brown IE Mashayekhi M Markiewicz M Alegre ML Gajewski TF 《Apoptosis : an international journal on programmed cell death》2005,10(1):5-11
Maintenance of a sufficient population of naïve CD8+ T cells in the peripheral lymphoid compartment is critical for immunocompetence. Peripheral T cell number is a function of T cell generation, survival, and death. Homeostasis, a critical balance between survival and death, must exist to prevent either lymphopenia or lymphocytosis. In the current review, we discuss known requirements for the survival of naïve peripheral CD8+ T cells as well as mechanisms of death when survival signals are lost. We also discuss associations between survival and homeostasis-driven proliferation, and highlight the gaps in our knowledge of these critical processes. 相似文献
7.
Tamaki T Okada Y Uchiyama Y Tono K Masuda M Wada M Hoshi A Akatsuka A 《Histochemistry and cell biology》2007,128(4):349-360
In order to establish the practical isolation and usage of skeletal muscle-derived stem cells (MDSCs), we determined reconstitution
capacity of CD34−/CD45− (Sk-DN) cells as a candidate somatic stem cell source for transplantation. Sk-DN cells were enzymatically isolated from GFP
transgenic mice (C57/BL6N) skeletal muscle and sorted using fluorescence activated cell sorting (FACS), and expanded by collagen
gel-based cell culture with bFGF and EGF. The number of Sk-DN cells was small after sorting (2–8 × 104); however, the number increased 10–20 fold (2–16 × 105) after 6 days of expansion culture, and the cells maintained immature state and multipotency, expressing mRNAs for mesodermal
and ectodermal cell lineages. Transplantation of expanded Sk-DN cells into the severe muscle damage model (C57/BL6N wild-type)
resulted in the synchronized reconstitution of blood vessels, peripheral nerves and muscle fibers following significant recovery
of total muscle mass (57%) and contractile function (55%), whereas the non-cell-transplanted control group showed around 20%
recovery in both factors. These reconstitution capacities were supported by the intrinsic plasticity of Sk-DN cells that can
differentiate into muscular (skeletal muscle), vascular (pericyte, endothelial cell and smooth muscle) and peripheral nerve
(Schwann cells and perineurium) cell lineages that was revealed by transplantation to non-muscle tissue (beneath renal capsule)
and fluorescence in situ hybridization (FISH) analysis. 相似文献
8.
Godefroy E Wang Y Souleimanian NE Scotto L Stevanovic S Chen YT Valmori D Ayyoub M 《Cancer immunology, immunotherapy : CII》2007,56(8):1183-1192
Proteins encoded by genes of the SSX family are specifically expressed in tumors and are therefore relevant targets for cancer immunotherapy. One of the first identified family members, SSX-1, is expressed in a large fraction of synovial sarcomas as a fusion protein together with the product of the SYT gene. In addition, the full-length SSX-1 antigen is frequently expressed in tumors of several other histological types such as sarcoma, melanoma, hepatocellular carcinoma, ovarian cancer and myeloma. To date, however, SSX-1 specific T cell responses have not been investigated and no SSX-1 derived T cell epitopes have been described. Here, we have assessed the presence of CD4(+) T cells directed against the SSX-1 antigen in circulating lymphocytes of cancer-free individuals. After a single in vitro stimulation with a pool of peptides spanning the entire SSX-1 protein we could detect and isolate SSX-1-specific CD4(+) T cells from 5/5 donors analyzed. SSX-1-specific polyclonal populations isolated from these cultures recognized peptides located in three distinct regions of the protein containing clusters of sequences with significant predicted binding to frequently expressed MHC class II alleles. Characterization of specific clonal CD4(+) T cell populations derived from one donor allowed the identification of several naturally processed epitopes recognized in association with HLA-DR. These data document the existence of a significant repertoire of CD4(+) T cells specific for SSX-1 derived sequences in circulating lymphocytes of any individual that can be exploited for the development of both passive and active immunotherapeutic approaches to control disease evolution in cancer patients. 相似文献
9.
10.
Torres ML Ortega F Cuaranta I González J Sanchez-Armass S 《Neurochemical research》2008,33(8):1574-1581
The Na+/H+ exchanger has been the only unequivocally demonstrated H+-transport mechanism in the synaptosomal preparation. We had previously suggested that a Cl−–H+ symporter (in its acidifying mode) is involved in cytosolic pH regulation in the synaptosomal preparation. Supporting this
suggestion, we now show that: (1) when synaptosomes are transferred from PSS to either gluconate or sulfate solutions, the
Fura-2 ratio remains stable instead of increasing as it does in 50 mM K solution. This indicates that these anions do not
promote a plasma membrane depolarization. (2) Based in the recovery rate from the cytosolic alkalinization, the anionic selectivity
of the Cl−–H+ symporter is NO3− > Br− > Cl− >> I− = isethionate = sulfate = methanesulfonate = gluconate. (3) PCMB 10 μM inhibits the gluconate-dependent alkalinization by
30 ± 6%. (4) Neither Niflumic acid, 9AC, Bumetanide nor CCCP inhibits the recovery from the cytosolic alkalinization.
Special issue article in honor of Dr. Ricardo Tapia. 相似文献
11.
Maria Giovanna di Bari M. E. Christine Lutsiak Shinji Takai Sven Mostböck Benedetto Farsaci Roshanak Tolouei Semnani Lalage M. Wakefield Jeffrey Schlom Helen Sabzevari 《Cancer immunology, immunotherapy : CII》2009,58(11):1809-1818
This study demonstrates that CD8+ T cells in the tumor microenvironment display reduced functionality and hyporesponsiveness. TGF-β contributed markedly to
the tumor-infiltrating CD8+ T cells’ (TILs) reduced functionality, which could be reversed using a small molecule TGF-β inhibitor. Upon T-cell receptor
(TCR) activation, the activation of ITK and ERK kinases were reduced in CD8+ TILs, as compared to splenic CD8+ T cells: TGF-β inhibitor could reverse this phenomenon. This study demonstrates for the first time the association of the
Spred-1 gene, an inhibitor of the Ras/MAPK pathway, with CD8+ TILs and TGF-β activity. Spred-1 was upregulated in CD8+ TILs and TGF-β enhanced the expression of Spred-1 in effector/memory CD8+ T cells and not in rested/memory CD8+ T cells. Based on these findings, this study supports the hypothesis that TGF-β mediates an inhibitory mechanism on CD8+ TILs involving TCR-signaling blockade and the upregulation of Spred-1, thus implicating Spred-1 as a potential new target
for future anti-tumor immune studies.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
M. G. di Bari and M. E. C. Lutsiak contributed equally to this work. 相似文献
12.
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
13.
NKT cells, na?ve CD4(+) T cells, and TCR-gammadelta T cells belong to distinct T cell lineages but all express T cell receptors generated through random combinatorial joining of V-(D)-J genes. These distinct lineage T cells also possess the property of promptly activating the IL-4 gene upon T cell receptor stimulation. A comparative accounting of features as they pertain to IL-4 inducibility in these three distinct lineage T cells is provided here. 相似文献
14.
Minu K. Srivastava Jacobus J. Bosch James A. Thompson Bruce R. Ksander Martin J. Edelman Suzanne Ostrand-Rosenberg 《Cancer immunology, immunotherapy : CII》2008,57(10):1493-1504
BACKGROUND: Advanced non-small cell lung cancer (NSCLC) remains an incurable disease. Immunotherapies that activate patients' T cells against resident tumor cells are being developed; however, these approaches may not be effective in NSCLC patients due to tumor-induced immune suppression. A major cause of immune suppression is myeloid-derived suppressor cells (MDSC). Because of the strategic role of CD4(+) T lymphocytes in the activation of cytotoxic CD8(+) T cells and immune memory, we are developing cell-based vaccines that activate tumor-specific CD4(+) T cells in the presence of MDSC. The vaccines are NSCLC cell lines transfected with costimulatory (CD80) plus major histocompatibility complex class II (MHC II) genes that are syngeneic to the recipient. The absence of invariant chain promotes the presentation of endogenously synthesized tumor antigens, and the activation of MHC II-restricted, tumor-antigen-specific CD4(+) T cells. METHODS: Potential vaccine efficacy was tested in vitro by priming and boosting peripheral blood mononuclear cells from ten NSCLC patients who had varying levels of MDSC. CD4(+) T cell activation was quantified by measuring Type 1 and Type 2 cytokine release. RESULTS: The vaccines activated CD4(+) T cells from all ten patients, despite the presence of CD33(+)CD11b(+) MDSC. Activated CD4(+) T cells were specific for NSCLC and did not cross-react with tumor cells derived from non-lung tissue or normal lung fibroblasts. CONCLUSIONS: The NSCLC vaccines activate tumor-specific CD4(+) T cells in the presence of potent immune suppression, and may be useful for the treatment of patients with NSCLC. 相似文献
15.
Carter BZ Mak DH Morris SJ Borthakur G Estey E Byrd AL Konopleva M Kantarjian H Andreeff M 《Apoptosis : an international journal on programmed cell death》2011,16(1):67-74
XIAP, a potent caspase inhibitor, is highly expressed in acute myeloid leukemia (AML) cells and contributes to chemoresistance.
A multi-center phase 1/2 trial of XIAP antisense oligonucleotide AEG35156 in combination with idarubicin/cytarabine was conducted
in 56 patients with relapsed/refractory AML. Herein we report the pharmacodynamic studies of the patients enrolled at M. D.
Anderson Cancer Center. A total of 13 patients were enrolled in our institution: five in phase 1 (12–350 mg/m2 AEG35156) and eight in phase 2 (350 mg/m2 AEG35156) of the protocol. AEG35156 was administered on 3 consecutive days and then weekly up to a maximum of 35 days. Blood
samples were collected from patients on days 1 through 5 and on day 28–35 post-chemotherapy for detection of XIAP levels and
apoptosis. AEG35156 treatment led to dose-dependent decreases of XIAP mRNA levels (42–100% reduction in phase 2 patients).
XIAP protein levels were reduced in all five samples measured. Apoptosis induction was detected in 1/4 phase 1 and 4/5 phase
2 patients. Importantly, apoptosis was most pronounced in CD34
+
38
−
AML stem cells and all phase 2 patients showing apoptosis induction in CD34
+
38
−
cells achieved response. We conclude that at 350 mg/m2, AEG35156 is effective in knocking down XIAP in circulating blasts accompanied by the preferential induction of apoptosis
in CD34
+
38
−
AML stem cells. 相似文献
16.
The majority of cells infected with the human immunodeficiency virus are activated CD4+ T cells, which can be treated with antiretoviral drugs. However, an obstacle to eradication is the presence of viral reservoirs, such as latently infected CD4+ T cells. Such cells may be less susceptible to antiretroviral drugs and may persist at low levels during treatment. We introduce a model of impulsive differential equations that describe T cell and drug interactions. We make the extreme assumption that latently infected cells are unaffected by drugs, in order to answer the research question: Can the viral reservoir of latently infected cells be eradicated using current antiretroviral therapy? We analyse the model in both the presence and absence of drugs, showing that, if the frequency of drug taking is sufficiently high, then the number of uninfected CD4+ T cells approaches the number of T cells in the uninfected immune system. In particular, this implies that the latent reservoir will be eliminated. It follows that, with sufficient application of drugs, latently infected cells cannot sustain a viral reservoir on their own. We illustrate the results with numerical simulations. 相似文献
17.
Zloza A Jagoda MC Lyons GE Graves MC Kohlhapp FJ O'Sullivan JA Lacek AT Nishimura MI Guevara-Patiño JA 《Cancer immunology, immunotherapy : CII》2011,60(2):291-297
CD8+ T cell function depends on a finely orchestrated balance of activation/suppression signals. While the stimulatory role of
the CD8 co-receptor and pleiotropic capabilities of TGF-β have been studied individually, the influence of CD8 co-receptor
on TGF-β function in CD8+ T cells is unknown. Here, we show that while CD8 enhances T cell activation, it also enhances susceptibility to TGF-β-mediated
immune suppression. Using Jurkat cells expressing a full-length, truncated or no αβCD8 molecule, we demonstrate that cells
expressing full-length αβCD8 were highly susceptible, αβCD8-truncated cells were partially susceptible, and CD8-deficient
cells were completely resistant to suppression by TGF-β. Additionally, we determined that inhibition of Lck rendered mouse
CD8+ T cells highly resistant to TGF-β suppression. Resistance was not associated with TGF-β receptor expression but did correlate
with decreased Smad3 and increased Smad7 levels. These findings highlight a previously unrecognized third role for CD8 co-receptor
which appears to prepare activated CD8+ T cells for response to TGF-β. Based on the important role which TGF-β-mediated suppression plays in tumor immunology, these
findings unveil necessary considerations in formulation of CD8+ T cell-related cancer immunotherapy strategies. 相似文献
18.
We are developing vaccines that activate tumor-specific CD4+ T cells. The cell-based vaccines consist of MHC class I+ tumor cells that are genetically modified to express syngeneic MHC class II and costimulatory molecules. Previous studies demonstrated that treatment of mice with established tumors with these vaccines resulted in regression of solid tumors, reduction of metastatic disease, and increased survival time. Optimal vaccines will prime naïve T cells and activate T cells to tumor peptides derived from diverse subcellular compartments, since potential tumor antigens may reside in unique cellular locales. To determine if the MHC class II / costimulatory molecule vaccines fulfill these conditions, the vaccines have been tested for their ability to activate antigen-specific, naïve, transgenic CD4+ T lymphocytes. MHC class II+CD80+ vaccine cells were transfected with hen eggwhite lysozyme targeted to the cytosol, nuclei, mitochondria, or endoplasmic reticulum, and used as antigen-presenting cells to activate I-Ak–restricted, lysozyme-specific CD4+ 3A9 transgenic T cells. Regardless of the cellular location of lysozyme, the vaccines stimulated release of high levels of IFN- and IL-2. If the vaccines coexpressed the MHC class II accessory molecule invariant chain, then IFN- and IL-2 release was significantly reduced. These studies demonstrate that in the absence of invariant chain the MHC class II and CD80 tumor cell vaccines (1) function as antigen-presenting cells to activate naïve, tumor-specific CD4+ cells to endogenously synthesized tumor antigens; (2) polarize the activated CD4+ T cells toward a type 1 response; and (3) present epitopes derived from varied subcellular locales.Abbreviations APC
antigen-presenting cells
- CIITA
MHC class II transactivator
- CytoHEL
HEL targeted to cytoplasm
- ER
endoplasmic reticulum
- ErHEL
HEL targeted to ER
- HEL
hen eggwhite lysozyme
- 3A9
HEL46–61–specific, I-Ak–restricted TCR
- Hph
hygromycin
- Ii
invariant chain
- MAb
monoclonal antibody
- MitoHEL
HEL targeted to mitochondria
- NucHEL
HEL targeted to nucleus
- Puro
puromycin
- TG
transgenic
- Zeo
Zeocin 相似文献
19.
20.
Hiramatsu Y Hosono A Konno T Nakanishi Y Muto M Suyama A Hachimura S Sato R Takahashi K Kaminogawa S 《Cytotechnology》2011,63(3):307-317
We have investigated the immunomodulatory mechanisms of Bifidobacterium pseudocatenulatum JCM7041 (Bp) as model of probiotics following oral administration to mice. This study was conducted with the aim of clarifying
the mechanism of immunomodulation induced by oral administration of probiotic bacteria through elucidation of the detailed
mechanism of transfer of orally administered bacterial cells within the body and the interaction between bacterial cells and
cells of the immune tissues. We observed the localization of Bp in mice following oral administration, showing that Bp was
surrounded by CD11c+ cells in Peyer’s patches (PP) and cecal patches (CP). These results indicated that Bp might induce CD11c+ cell-mediated immune responses directly. Furthermore, IL-10 and IL-12p40 production by Thy1.2− cells, including CD11c+ cells, increased significantly. Production of IL-10 and IL-12p40 by bone marrow-derived dendritic cells (BMDC) was significantly
increased by Bp stimulation. These results suggest that oral administration of Bp induces immune responses directly following
capture by CD11c+ dendritic cells (DCs). Subsequently, we observed oral administration of Bp for 1 week induced IgA and IgA-associated cytokine
production by CP and PP cells, suggesting that Bp induced DC-mediated immune responses on CP as well as PP. 相似文献