共查询到20条相似文献,搜索用时 15 毫秒
1.
Tadafumi Yokoyama Ayumi Yoshizaki Karen L. Simon Martha R. Kirby Stacie M. Anderson Fabio Candotti 《PloS one》2015,10(10)
The Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency characterized by recurrent infections, thrombocytopenia, eczema, and high incidence of malignancy and autoimmunity. The cellular mechanisms underlying autoimmune complications in WAS have been extensively studied; however, they remain incompletely defined. We investigated the characteristics of IL-10-producing CD19+CD1dhighCD5+ B cells (CD1dhighCD5+ Breg) obtained from Was gene knockout (WKO) mice and found that their numbers were significantly lower in these mice compared to wild type (WT) controls. Moreover, we found a significant age-dependent reduction of the percentage of IL-10-expressing cells in WKO CD1dhighCD5+ Breg cells as compared to age-matched WT control mice. CD1dhighCD5+ Breg cells from older WKO mice did not suppress the in vitro production of inflammatory cytokines from activated CD4+ T cells. Interestingly, CD1dhighCD5+ Breg cells from older WKO mice displayed a basal activated phenotype which may prevent normal cellular responses, among which is the expression of IL-10. These defects may contribute to the susceptibility to autoimmunity with age in patients with WAS. 相似文献
2.
Our previous result indicated that memory-like human natural killer (NK) cells from TB pleural fluid cells (PFCs) produced large amounts of IFN-γ in response to Bacille Calmette Guerin (BCG). Furthermore, recent studies have shown that human lymphoid tissues harbored a unique NK cell subset that specialized in production of interleukin (IL)-22, a proinflammatory cytokine that mediates host defense against pathogens. Yet little information was available with regard to the properties of IL-22 production by memory-like human NK cells. In the present study, we found that cytokines IL-15 induced and IL-12 enhanced the levels of IL-22 by NK cells from TB PFCs. In addition, IL-22 but not IL-17 was produced by NK cells from PFCs in response to BCG and M.tb-related Ags. More importantly, the subset of specific IL-22-producing NK cells were distinct from IFN-γ-producing NK cells in PFCs. CD45RO+ or CD45RO- NK cells were sorted, co-cultured with autologous monocytes and stimulated with BCG for the production of IL-22. The result demonstrated that CD45RO+ but not CD45RO- NK cells produced significantly higher level of IL-22. Anti-IL-12Rβ1 mAbs (2B10) partially inhibit the expression of IL-22 by NK cells under the culture with BCG. Consistently, BCG specific IL-22-producing NK cells from PFCs expressed CD45ROhighNKG2Dhighgranzyme Bhigh. In conclusion, our data demonstrated that memory-like antigen-specific CD45RO+ NK cells might participate in the recall immune response for M. tb infection via producing IL-22, which display a critical role to fight against M. tb. 相似文献
3.
Tumor-derived Fas ligand induces toxicity in lymphoid organs and plays an important role in successful chemotherapy 总被引:7,自引:0,他引:7
Nagarkatti N 《Cancer immunology, immunotherapy : CII》2000,49(1):46-55
Recent studies have suggested that Fas ligand (FasL+) tumor cells can induce apoptosis in Fas+ T cells. However, the effect of growth of FasL+ tumors in vivo, on lymphoid tissues of the host is not clear and therefore was the subject of this investigation. Injection
of FasL+ LSA tumor caused a significant decrease in cellularity of the thymus and spleen, resulting from marked apoptosis, in syngeneic
C57BL/6+/+ (wild-type) but not C57BL/6-lpr/lpr (Fas-deficient) mice. The tumor-induced toxicity resulted from tumor-derived rather than host-derived FasL, inasmuch as LSA
tumor growth in C57BL/6-gld/gld (FasL-defective) mice, induced marked apoptosis and toxicity in the thymus and spleen. The LSA tumor growth induced a significant
decrease in the percentage of CD4+CD8+ T cells in the thymus of C57BL/6+/+ mice and an increase in the percentage of CD4+, CD8+ and CD4−CD8− T cells. Of the four subpopulations tested, the CD4+CD8+ T cells showed maximum apoptosis. The LSA (FasL+) but not P815(FasL−) tumor cell lysates and culture supernatants induced marked apoptosis in Fas+ thymocytes, when tested both in vitro and in vivo. The LSA-tumor-induced apoptosis in vitro was inhibited by antibodies against
FasL or by caspase and other inhibitors of apoptosis. Chemotherapy of LSA-tumor-bearing C57BL/6+/+ mice at advanced stages
of tumor growth failed to cure the mice, whereas, more than 80% of LSA-tumor-bearing C57BL/6-lpr/lpr mice, similarly treated, survived. Together, the current study demonstrates that FasL produced by LSA tumor cells is functional
in vivo and can cause severe toxicity in lymphoid organs of the host. Also, Fas/FasL interactions may play an important role
in the successful chemotherapy of FasL-bearing tumor.
Received: 31 August 1999 / Accepted: 12 November 1999 相似文献
4.
Hyuk Soon Kim Jun Ho Lee Hee Dong Han A-Ram Kim Seung Taek Nam Hyun Woo Kim Young Hwan Park Dajeong Lee Min Bum Lee Yeong Min Park Hyung Sik Kim Young Mi Kim Ji Chang You Wahn Soo Choi 《BMB reports》2015,48(1):54-59
IL-10-producing B (Breg) cells regulate various immune responses. However, their phenotype remains unclear. CD40 expression was significantly increased in B cells by LPS, and the Breg cells were also enriched in CD40hiCD5+ B cells. Furthermore, CD40 expression on Breg cells was increased by IL-10, CD40 ligand, and B cell-activating factor, suggesting that CD40hi is a common phenotype of Breg cells. LPS-induced CD40 expression was largely suppressed by an anti-IL-10 receptor antibody and in IL-10−/−CD5+CD19+ B cells. The autocrine effect of IL-10 on the CD40 expression was largely suppressed by an inhibitor of JAK/STAT3. In vivo, the LPS treatment increased the population of CD40hiCD5+ Breg cells in mice. However, the population of CD40hiCD5+ B cells was minimal in IL-10−/− mice by LPS. Altogether, our findings show that Breg cells are largely enriched in CD40hiCD5+ B cells and the autocrine effect of IL-10 is critical to the formation of CD40hiCD5+ Breg cells. [BMB Reports 2015; 48(1): 54-59] 相似文献
5.
Catriona T. Prendergast David E. Sanin Adrian P. Mountford 《PLoS neglected tropical diseases》2016,10(8)
In a murine model of repeated exposure of the skin to infective Schistosoma mansoni cercariae, events leading to the priming of CD4 cells in the skin draining lymph nodes were examined. The dermal exudate cell (DEC) population recovered from repeatedly (4x) exposed skin contained an influx of mononuclear phagocytes comprising three distinct populations according to their differential expression of F4/80 and MHC-II. As determined by gene expression analysis, all three DEC populations (F4/80-MHC-IIhigh, F4/80+MHC-IIhigh, F4/80+MHC-IIint) exhibited major up-regulation of genes associated with alternative activation. The gene encoding RELMα (hallmark of alternatively activated cells) was highly up-regulated in all three DEC populations. However, in 4x infected mice deficient in RELMα, there was no change in the extent of inflammation at the skin infection site compared to 4x infected wild-type cohorts, nor was there a difference in the abundance of different mononuclear phagocyte DEC populations. The absence of RELMα resulted in greater numbers of CD4+ cells in the skin draining lymph nodes (sdLN) of 4x infected mice, although they remained hypo-responsive. Using mice deficient for IL-4Rα, in which alternative activation is compromised, we show that after repeated schistosome infection, levels of regulatory IL-10 in the skin were reduced, accompanied by increased numbers of MHC-IIhigh cells and CD4+ T cells in the skin. There were also increased numbers of CD4+ T cells in the sdLN in the absence of IL-4Rα compared to cells from singly infected mice. Although their ability to proliferate was still compromised, increased cellularity of sdLN from 4x IL-4RαKO mice correlated with reduced expression of Fas/FasL, resulting in decreased apoptosis and cell death but increased numbers of viable CD4+ T cells. This study highlights a mechanism through which IL-4Rα may regulate the immune system through the induction of IL-10 and regulation of Fas/FasL mediated cell death. 相似文献
6.
Yumei Zhang Yanyan Jiang Yanjuan Wang Hua Liu Yujuan Shen Zhongying Yuan Yuan Hu Yuxin Xu Jianping Cao 《International journal of biological sciences》2015,11(9):1049-1055
The current knowledge of immunological responses to schistosomiasis is insufficient for the development of vaccine and therapies. The role of T follicular helper (Tfh) cells in schistosome infections is not fully defined. The frequency of circulating Tfh cells and serum cytokine levels were analyzed in 11 patients with chronic schistosomiasis and 10 healthy controls (HC), who reside in an endemic area for Schistosomiasis japonicum. Significantly higher frequencies of circulating CXCR5+ CD4+ Tfh cells and higher expression levels of ICOS and PD-1 in CXCR5+ CD4+ Tfh cells were observed in patients with chronic schistosomiasis compared to HC. The levels of IL-21 in serum and the expression of IL-21 mRNA were higher in chronic schistosomiasis patients than in HC. Moreover, the frequency of circulating PD-1high CXCR5+ CD4+ Tfh cells positively correlated with the levels of IL-21 in serum from patients with chronic schistosomiasis. A positive correlation was also found between the frequency of PD-1high CXCR5+ CD4+ Tfh cells and the levels of soluble egg antigen (SEA)-specific antibodies in serum samples from the patient group. Our study is the first regarding Tfh cells in chronic human schistosomiasis and the finding indicate that PD-1high CXCR5+ CD4+Tfh cells might play an important role in the production of specific antibodies in schistosomiasis. This study contributes to the understanding of immune response to schistosomiasis and may provide helpful support in vaccine development. 相似文献
7.
Bo Tang Wei Wu Xiaowei Wei Yang Li Gang Ren Wenhai Fan 《The Journal of biological chemistry》2014,289(50):34595-34600
Therapeutic outcomes of glioma are currently not encouraging. Tumor tolerance plays an important role in the pathogenesis of glioma. It is reported that micro RNAs (miR) are associated with tumor development. This study aims to investigate the role of miR-92a in the development of tolerant natural killer T (NKT) cells. In this study, U87 cells (a human glioma cell line) and primary glioma cells were prepared. The assessment of miR-92a was performed by real time RT-PCR. The expression of interleukin (IL)-10 and IL-6 in NKT cells was evaluated by flow cytometry. Results showed that abundant IL-6+ IL-10+ NKT cells were detected in glioma tissue. Cultures of glioma cells and NKT cells induced the expression of IL-6 and IL-10 in NKT cells. Glioma cells expressed miR-92a; the latter played a critical role in the induction of IL-6 and IL-10 expression in NKT cells. The expression of the antitumor molecules, including perforin, Fas ligand, and interferon-γ, was significantly attenuated compared with control NKT cells. The IL-6+ IL-10+ NKT cells showed less capability in the induction of apoptosis in glioma cells, but showed the immune suppressor functions on CD8+ T cell activities. We conclude that glioma-derived miR-92a induces IL-6+ IL-10+ NKT cells; this fraction of NKT cells can suppress cytotoxic CD8+ T cells. 相似文献
8.
Jue Xie Dawei Cui Yan Liu Jie Jin Hongyan Tong Lei Wang Guoxiang Ruan Yun Lu Huiming Yuan 《International journal of biological sciences》2015,11(2):220-229
Background: Idiopathic thrombocytopenic purpura (ITP) is a primary autoimmune disease with a decreased platelet count caused by platelet destruction mediated mainly by platelet antibodies. T follicular helper (TFH) cells have demonstrated important roles in autoimmune diseases. The aim of this study is to explore the might role of TFH cells in the patients of ITP.Methods: Twenty-three ITP patients and 12 healthy controls (HC) were enrolled in this study. The frequency of circulating TFH cells in both the patients and HC was analyzed by flow cytometry. Serum interleukin (IL)-21 and IL-6 levels were measured using ELISA, and platelet antibodies were tested using a solid phase technique. Additionally, IL-21, IL-6, Bcl-6 and c-Maf mRNA expressions in peripheral blood mononuclear cells (PBMCs) were detected using real-time PCR.Results: The percentages of circulating CXCR5+ CD4+TFH cells with ICOShigh or PD-1high expression were significantly higher in the ITP patients than in the HC. Moreover, the frequencies of circulating CXCR5+ CD4+TFH cells with inducible costimulator (ICOS)high or programmed death-1 (PD-1)high expression were notably higher in ITP with platelet-antibody-positive ( ITP (+) ) patients than in ITP with platelet-antibody-negative ( ITP (-) ) patients and HC, as were the serum IL-21 and IL-6 levels (significant). Moreover, a positive correlation was found between the CXCR5+CD4+TFH cells with ICOShigh or PD-1high expression and the serum IL-21 levels of ITP (+) patients. Additionally, the mRNA expression levels of IL-21, IL-6, Bcl-6 and c-Maf were significantly increased in ITP patients, especially in ITP (+) patients.Conclusions: This study demonstrated TFH cells and effector molecules might play an important role in the pathogenesis of ITP, which are possible therapeutic targets in ITP patients. 相似文献
9.
Robert M. Paris Constantinos Petrovas Sara Ferrando-Martinez Eirini Moysi Kristin L. Boswell Eva Archer Takuya Yamamoto David Ambrozak Joseph P. Casazza Richard Haubrich Mark Connors Julie Ake Jerome H. Kim Richard A. Koup 《PloS one》2015,10(12)
The role of PD-1 expression on CD4 T cells during HIV infection is not well
understood. Here, we describe the differential expression of PD-1 in
CD127high CD4 T cells within the early/intermediate differentiated (EI)
(CD27highCD45RAlow) T cell population among uninfected and
HIV-infected subjects, with higher expression associated with decreased viral
replication (HIV-1 viral load). A significant loss of circulating
PD-1highCTLA-4low CD4 T cells was found specifically in the
CD127highCD27highCD45RAlow compartment, while
initiation of antiretroviral treatment, particularly in subjects with advanced
disease, reversed these dynamics. Increased HIV-1 Gag DNA was also found in
PD-1high compared to PD-1low ED CD4 T cells. In line with an
increased susceptibility to HIV infection, PD-1 expression in this CD4 T cell subset
was associated with increased activation and expression of the HIV co-receptor, CCR5.
Rather than exhaustion, this population produced more IFN-g, MIP1-a, IL-4, IL-10, and
IL-17a compared to PD-1low EI CD4 T cells. In line with our previous
findings, PD-1high EI CD4 T cells were also characterized by a high
expression of CCR7, CXCR5 and CCR6, a phenotype associated with increased in
vitro B cell help. Our data show that expression of PD-1 on
early-differentiated CD4 T cells may represent a population that is highly
functional, more susceptible to HIV infection and selectively lost in chronic HIV
infection. 相似文献
10.
Role of T‐bet,the master regulator of Th1 cells,in the cytotoxicity of murine CD4+ T cells
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Koji Eshima Kana Misawa Chihiro Ohashi Kazuya Iwabuchi 《Microbiology and immunology》2018,62(5):348-356
11.
Baschuk N Utermöhlen O Gugel R Warnecke G Karow U Paulsen D Brombacher F Krönke M Deppert W 《Cancer immunology, immunotherapy : CII》2007,56(10):1625-1636
In this report we analyzed the impact of interleukin-4 (IL-4) on tumor-associated simian virus 40 (SV40) large T-antigen (TAg)-specific CD8+ cytotoxic T cells during rejection of syngeneic SV40 transformed mKSA tumor cells in BALB/c mice. Strikingly, challenge of naïve mice with low doses of mKSA tumor cells revealed a CD8+ T cell-dependent prolonged survival time of naïve IL-4?/? mice. In mice immunized with SV40 TAg we observed in IL-4?/? mice, or in wild type mice treated with neutralizing anti-IL-4 monoclonal antibody, a strongly enhanced TAg-specific cytotoxicity of tumor associated CD8+ T cells. The enhanced cytotoxicity in IL-4?/? mice was accompanied by a significant increase in the fraction of CD8+ tumor associated T-cells expressing the cytotoxic effector molecules granzyme A and B and in granzyme B-specific enzymatic activity. The data suggest that endogenous IL-4 can suppress the generation of CD8+ CTL expressing cytotoxic effector molecules especially when the antigen induces only a very weak CTL response. 相似文献
12.
Yoshiyuki Mishima Shunji Ishihara Akihiko Oka Nobuhiko Fukuba Naoki Oshima Hiroki Sonoyama Noritsugu Yamashita Yasumasa Tada Ryusaku Kusunoki Ichiro Moriyama Takafumi Yuki Kousaku Kawashima Yoshikazu Kinoshita 《PloS one》2016,11(1)
Background
CD5+ B cells are a type of regulatory immune cells, though the involvement of this B cell subset in intestinal inflammation and immune regulation is not fully understood.Methods
We examined the distribution of CD5+ B cells in various mouse organs. Expression levels of CD11b, IgM, and toll-like receptor (TLR)-4 and -9 in B cells were evaluated. In vitro, TLR-stimulated IL-10 production by colonic lamina propria (LP) CD5+ and CD5- B cells was measured. In vivo, mice with acute or chronic dextran sulfate sodium (DSS)-induced colonic injury were examined, and the frequency of colonic LP CD5+ B cells in those was assessed by flow cytometry.Results
The expression level of TLR9 was higher in colonic LP CD5+ B cells as compared to CD5- B cells. Colonic LP CD5+ B cells produced greater amounts of IL-10 following stimulation with TLR ligands, especially TLR9, as compared with the LP CD5- B cells. Acute intestinal inflammation transiently decreased the frequency of colonic LP CD5+ B cells, while chronic inflammation induced a persistent decrease in colonic LP CD5+ B cells and led to a CD5- B cell-dominant condition.Conclusion
A persistent altered mucosal B cell population caused by chronic gut inflammation may be involved in the pathogenesis of inflammatory bowel diseases. 相似文献13.
In the current study of Mycobacterium tuberculosis (MTB)-specific T and B cells, we found that MTB-specific peptides from early secreted antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) induced the expression of IL-21 predominantly in CD4+ T cells. A fraction of IL-21-expressing CD4+ T cells simultaneously expressed Th1 cytokines but did not secrete Th2 or Th17 cytokines, suggesting that MTB-specific IL-21-expressing CD4+ T cells were different from Th1, Th2 and Th17 subpopulations. The majority of MTB-specific IL-21-expressing CD4+ T cells co-expressed IFN-γ and IL-21+IFN-γ+CD4+ T cells exhibited obviously polyfunctionality. In addition, MTB-specific IL-21-expressing CD4+ T cells displayed a CD45RO+CD62LlowCCR7lowCD40LhighICOShigh phenotype. Bcl-6-expression was significantly higher in IL-21-expressing CD4+ T cells than IL-21-CD4+ T cells. Moreover, IL-12 could up-regulate MTB-specific IL-21 expression, especially the frequency of IL-21+IFN-γ+CD4+ T cells. Taken together, our results demonstrated that MTB-specific IL-21+IFN-γ+CD4+ T cells from local sites of tuberculosis (TB) infection could be enhanced by IL-12, which have the features of both Tfh and Th1 cells and may have an important role in local immune responses against TB infection. 相似文献
14.
Rodolphe Thiébaut Julia Drylewicz Mélanie Prague Christine Lacabaratz Stéphanie Beq Ana Jarne Thérèse Croughs Rafick-Pierre Sekaly Michael M. Lederman Irini Sereti Daniel Commenges Yves Lévy 《PLoS computational biology》2014,10(5)
Exogenous Interleukin-7 (IL-7), in supplement to antiretroviral therapy, leads to a substantial increase of all CD4+ T cell subsets in HIV-1 infected patients. However, the quantitative contribution of the several potential mechanisms of action of IL-7 is unknown. We have performed a mathematical analysis of repeated measurements of total and naive CD4+ T cells and their Ki67 expression from HIV-1 infected patients involved in three phase I/II studies (N = 53 patients). We show that, besides a transient increase of peripheral proliferation, IL-7 exerts additional effects that play a significant role in CD4+ T cell dynamics up to 52 weeks. A decrease of the loss rate of the total CD4+ T cell is the most probable explanation. If this effect could be maintained during repeated administration of IL-7, our simulation study shows that such a strategy may allow maintaining CD4+ T cell counts above 500 cells/µL with 4 cycles or fewer over a period of two years. This in-depth analysis of clinical data revealed the potential for IL-7 to achieve sustained CD4+ T cell restoration with limited IL-7 exposure in HIV-1 infected patients with immune failure despite antiretroviral therapy. 相似文献
15.
Alan Winkelstein Leslie D. Weaver Nan Salva Laurie L. Machen 《Cancer immunology, immunotherapy : CII》1990,32(2):110-116
Summary Interleukin-2 (IL-2) is capable of both stimulating an in vitro lymphoproliferative response and augmenting non-major-histocompatibility-complex-(MHC)-restricted cytotoxicity. However, there are conflicting reports about the phenotypes of responding cells. In the present studies, we determined phenotypes of Ficoll/Hypaque-separated peripheral blood mononuclear cells stimulated with 50, 100 or 1000 U/ml IL-2; analyses were performed after 1, 3 and 5 weeks. With all concentrations, there was a progressive increase in CD3+ cells; after 3–5 weeks more than 90% of the cells reacted with this antibody. However, the proportions of CD4+ and CD8+ cells proved to be a function of the IL-2 concentration. Cultures containing 50 U/ml or 100 U/ml favored the expansion of the CD4+ subset. By contrast, in cultures stimulated with 1000 U/ml, CD8+ cells predominated. At baseline, CD8+ cells comprised 28±2%; after 3 weeks, this value increased to 51±5%. In addition, the proportion of CD56+ (Leu19, NKH-1) cells depended on the amount of IL-2. At 50 U/ml, there was no appreciable change in CD56+ cells. However, at 1000 U/ml, CD56+ cells increased from 17±1% (day 0) to 39±4% (3 weeks). This increase was primarily due to an expansion of the CD3+ CD56+ subset (non-NMC restricted cytotoxic T cells). By contrast, natural killer (NK) cells, as measured by the CD16 antibody, steadily declined at all IL-2 concentrations.These studies were supported by a grant from the National Cancer Institute, NIH (RO1 CA24429-15) 相似文献
16.
T lymphocyte secretion of interleukin-13 (IL-13) in response to different activation signals was characterized in vitro. IL-13
release was investigated when virus transformed B lymphocytes or acute myelogenous leukaemia (AML) blasts were used as accessory
cells during T cell activation. First, a majority of both CD4+ and CD8+ TCRαβ+ T lymphocyte clones, derived from normal individuals and bone marrow transplant recipients, secreted IL-13 in response to
a standardized mitogenic activation signal (phytohaemagglutinin+IL-2+ B lymphocyte accessory cells). The CD4+ cells showed significantly higher IL-13 levels than the CD8+ subsets. Second, when leukaemic accessory cells (more than 95% AML blasts) were used during T cell activation, IL-13 was
released both during alloactivation of normal T lymphocytes and during mitogen activation of posttransplant T cells. Third,
when normal T lymphocytes were stimulated with allogeneic AML blasts, addition of IL-13-neutralizing monoclonal antibodies
decreased interferon γ levels. Although addition of IL-13-neutralizing antibodies did not alter granulocyte-colony-stimulating
factor secretion by allostimulating AML blasts, altered blast proliferation was detected for certain patients. Thus, most
T cell clones can release IL-13, and IL-13 can modulate cytokine responses during T cell recognition of allogeneic AML cells.
Received: 24 April 1997 / Accepted: 24 July 1997 相似文献
17.
Rajia Bahri Annalena Bollinger Thomas Bollinger Zane Orinska Silvia Bulfone-Paus 《PloS one》2012,7(9)
Regulatory CD8+ T cells are critical for self-tolerance and restricting excessive immune responses. The variety of immune functions they fulfill, the heterogeneity of their phenotype, and the mechanism of action are still poorly understood. Here we describe that regulatory CD8+ T cells exhibiting immunosuppressive actions in vitro and in vivo are recognized as CD38high T cells and present in naive mice. CD38 is a glycosylated membrane protein with ectonucleotidase properties. CD8+CD38high (CD44+CD122+CD62Lhigh) lymphocytes suppress CD4+ effector T-cell proliferation in an antigen-non specific manner via IFN-γ. While direct cell-to-cell contact is needed for this suppressor activity, it is independent of membrane-bound TGF-β and granzyme B release. IL-15 potentiates the suppressive activity of CD8+CD38high T cells and controls their survival and expansion. In humans CD8+CD38high T cells inhibit CD4+ effector T cell proliferation. In vivo, CD8+CD38high, but not CD8+CD38− T cells mitigate murine experimental autoimmune encephalomyelitis (EAE) by reducing the clinical score and delaying disease occurrence. EAE suppression is enhanced by pre-treatment of CD8+CD38high T cells with IL-15. These findings add evidence that the expression of ectoenzyme receptor family members positively correlates with suppressor functions and identifies CD8+CD38high T cells as potential inhibitors of excessive immune responses. 相似文献
18.
Yusuke Nakanishi Akira Hosono Yasuhiro Hiramatsu Teiji Kimura Ryo Nakamura Shuichi Kaminogawa 《Cytotechnology》2005,47(1-3):69-77
We demonstrate immunomodulatory effects, especially those involving murine intestinal IgA secretion, in Peyer's patch cells
following oral administration of Bifidobacterium immunomodulator (BIM) derived from sonicated B. pseudocatenulatum 7041. BALB/c mice were administered BIM orally for 7 consecutive days. The PP cells demonstrated upregulated secretion of
total IgA including BIM-specific IgA following BIM administration. In observing the response of PP cells co-cultured with
BIM, we found enhanced secretion of interferon-γ (IFN-γ) and interleukin (IL)-6 in the CD4+ T cells. In contrast, IL-12 secretion by Thy1.2− PP cells was enhanced, but secretion of IFN-γ, IL-5, and IL-6 was not significantly affected. Furthermore, the population
of CD4+ CD45RBhigh T cells in PP increased following oral administration of BIM. These data suggest that CD4+ T cells were affected by BIM administration. Overall, the results show that oral administration of BIM induced CD4+ PP cells to change their expression of cell surface antigen and cytokine production. 相似文献
19.
Catuxa Prado Banesa de Paz Patricia López Jesús Gómez Javier Rodríguez-Carrio Ana Suárez 《Cytokine》2013,61(1):90-96
In this work we studied CD4+FOXP3+ populations in systemic lupus erythematosus (SLE) and the relationship with Th cytokine production. We found an increment in CD25?FOXP3+ population in SLE associated with CD4+ downregulation and disease progression. CD25low cells were also upregulated and showed increased percentages of FOXP3+ and CD127?/low cells, supporting the activated status of SLE lymphocytes. Despite the normal levels of CD25highFOXP3+ cells, the negative correlations observed in controls with the frequency of IFNγ, TNFα and IL-10 secreting cells were disrupted in patients, supporting a defective Treg function. Also, CD25high cells showed an altered balance in the production of these cytokines. In addition, CD25highFOXP3+ cells correlated directly with IL-17A and IL-8 but not with TGFβ in SLE. The increased proportion of IL-17+ cells among the CD25high subset and the positive correlation between IL-17 levels and Treg cells suggest a trans-differentiation of Treg into Th17 cells in SLE. 相似文献
20.
Díaz-Montero CM El Naggar S Al Khami A El Naggar R Montero AJ Cole DJ Salem ML 《Cancer immunology, immunotherapy : CII》2008,57(4):563-572
During the antigen-dependant activation process several subsets CD8+ T cells appear with different phenotypic and functional characteristics. Recent studies indicate that the state of T cell differentiation radically affects their ability to effectively respond to tumor challenge, with early effector CD8+ T (CD62Lhigh) cells having better anti-tumor activity. Thus strategies aimed at optimizing the generation of such subpopulations could significantly enhance the effectiveness of adoptive cell therapy (ACT) for cancer. In this study, we show that priming of naïve CD8+ T cells in the presence of IL-12 selectively rescued early CD8+ CD62Lhi from activation induced cell death and resulted in the increased accumulation of this subset of CD8+ T cells. Furthermore, we demonstrated that IL-12 directly modulated the expression of CD62L on activated CD8+ T cells. When used for ACT, naïve CD8+ T cells primed in vitro in the presence of IL-12 showed superior anti-tumor activity toward B16 melanoma. Importantly, using the Pmel-1 model, priming pmel-1 cells in vitro with IL-12 reduced the state of functional tolerance associated with the non-mutated “self” tumor antigen gp100, as demonstrated by significant tumor responses in the absence of vaccination. Together, our results suggest that in vitro conditioning of naïve CD8+ T cells with IL-12 prior to ACT could significantly enhance their anti-tumor activity. 相似文献