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1.
BACKGROUND. The invasion and destruction of nonnecrotic muscle fibers by CD8+ cytotoxic T cells is considered a hallmark of polymyositis. In the cases of polymyositis reported so far, the autoinvasive CD8+ T cells expressed the common form of T-cell receptor for the recognition of antigen, the so-called alpha/beta T-cell receptor. We describe a 69-year-old man with polymyositis mediated by CD4-, CD8- T cells expressing the recently discovered, uncommon gamma/delta T-cell receptor. METHODS. We used immunofluorescence or immunoperoxidase techniques to study frozen sections of muscle from our patient, who had mild weakness of cervical and proximal limb muscles, and from control patients with polymyositis, inclusion-body myositis, dermatomyositis, or granulomatous myopathy with monoclonal antibodies against T-cell-related antigens (CD2, CD3, CD4, CD8, and gamma/delta T-cell receptor), B cells (CD22), major histocompatibility complex (MHC) and MHC-related antigens (MHC Class I, CD1a, CD1b, and CD1c), and the 65-kd heat-shock protein. The membrane contacts between the autoinvasive cells and the sarcolemma were investigated by electron microscopy. RESULTS. In the patient described here, but not in 28 others with inflammatory myopathies, myriad gamma/delta T cells surrounded and invaded nonnecrotic muscle fibers. All muscle fibers were highly reactive for MHC Class I antigen and the 65-kd heat-shock protein. Treatment with prednisone improved the clinical and histologic findings. CONCLUSIONS. Polymyositis can be mediated by gamma/delta T cells. This new form of polymyositis appears to be highly responsive to steroids. 相似文献
2.
《Immunological investigations》2013,42(6):965-976
Conjugation of the T cell receptor (TCR) with antigen/MHC proteins must be accompanied by conjugation of T cell counterreceptors (CD28 or CTLA-4) with costimulatory molecules CD80 or CD86 (B7-1 or B7-2) on antigen presenting cells (APC) to avert T cell anergy, and to provide essential signals for T cell activation and cytokine production. However, T cells and APC express changing patterns of counterreceptors and costimulatory molecules during the immune response. To determine the involvement of CD80 and CD86 in costimulation of T cell cytokine production, T cells were incubated with peritoneal exudate macrophages, which express CD80 and CD86, and stimulated in vitro for 48 or 72 hrs with anti-CD3 in the presence or absence of blocking antibody to CD80 or CD86. Alternatively, enriched anti-CD3 stimulated T cells were costimulated with antibody to CD28 and CTLA-4. Production of T cell IL-2, IL-4, and IL-5 was depressed in the presence of anti-CD86 but not anti-CD80. Production of IFN-γ was significantly blocked by either anti-CD80 and anti-CD86. Anti-CD28 was a potent costimulator of IFN-γ and IL-2 production, but a less potent costimulator of IL-4 and IL-5 production. The data suggest that T cell counterreceptors and APC costimulatory molecules act with varying efficacies at stimulating production of T cell cytokines. 相似文献
3.
Thomas M. Petro Swey-Shen A. Chen Robert B. Panther 《Immunological investigations》1995,24(6):965-976
Conjugation of the T cell receptor (TCR) with antigen/MHC proteins must be accompanied by conjugation of T cell counterreceptors (CD28 or CTLA-4) with costimulatory molecules CD80 or CD86 (B7-1 or B7-2) on antigen presenting cells (APC) to avert T cell anergy, and to provide essential signals for T cell activation and cytokine production. However, T cells and APC express changing patterns of counterreceptors and costimulatory molecules during the immune response. To determine the involvement of CD80 and CD86 in costimulation of T cell cytokine production, T cells were incubated with peritoneal exudate macrophages, which express CD80 and CD86, and stimulated in vitro for 48 or 72 hrs with anti-CD3 in the presence or absence of blocking antibody to CD80 or CD86. Alternatively, enriched anti-CD3 stimulated T cells were costimulated with antibody to CD28 and CTLA-4. Production of T cell IL-2, IL-4, and IL-5 was depressed in the presence of anti-CD86 but not anti-CD80. Production of IFN-γ was significantly blocked by either anti-CD80 and anti-CD86. Anti-CD28 was a potent costimulator of IFN-γ and IL-2 production, but a less potent costimulator of IL-4 and IL-5 production. The data suggest that T cell counterreceptors and APC costimulatory molecules act with varying efficacies at stimulating production of T cell cytokines. 相似文献
4.
Steiner K Waase I Rau T Dietrich M Fleischer B Bröker BM 《Clinical and experimental immunology》1999,115(3):451-457
CTLA-4 (CD152) is a surface molecule of activated T cells with sequence homology to CD28. Both molecules bind to the same ligands, B7.1 (CD80) and B7.2 (CD86) but have antagonistic functions. While CD28 is an important costimulator, CTLA-4 has an essential inhibitory function in maintaining the homeostasis of the immune system. Down-regulation of CD28 predominantly on CD8+ T cells has been described in HIV infection, but analysis of CTLA-4 is complicated by its low expression levels. Here we have used potent signal enhancement to study CTLA-4 on peripheral blood mononuclear cells (PBMC) during HIV infection. CTLA-4 was expressed only on T cells. Expression levels were significantly increased selectively on CD4+ T cells during all stages of HIV infection, while CTLA-4 expression on CD8+ T cells was always low. In contrast, after stimulation with the mitogen phytohaemagglutinin (PHA), CTLA-4 levels were strongly increased on T cells from controls but in T cells from HIV patients this response was severely impaired. Our data suggest that in HIV infection CD4+ and CD8+ T cells may be less responsive to B7 costimuli due to two different mechanisms: increase in CTLA-4 expression by CD4+ cells and down-regulation of CD28 by CD8+ cells. 相似文献
5.
Expression of costimulatory molecules CD80 and CD86 and their receptors CD28, CTLA-4 on malignant ascites CD3+ tumour-infiltrating lymphocytes (TIL) from patients with ovarian and other types of peritoneal carcinomatosis
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Melichar B Nash MA Lenzi R Platsoucas CD Freedman RS 《Clinical and experimental immunology》2000,119(1):19-27
6.
Höhn H Jülch M Pilch H Kortsik C Tully G Neukirch C Freitag K Maeurer M 《Clinical and experimental immunology》2003,131(1):102-110
In response to antigenic stimulation, naive MHC-class I restricted and antigen-specific CD8+ CD45RA+ CD28+ T cells undergo clonal expansion, differentiate into CD8+ CD45RO+ memory T cells and convert to CD8+ CD45RA+ CD28- T cells displaying potent immune effector functions upon re-encounter with the nominal antigen. We show that the effector CD8+ CD45RA+ CD28- T cell subset is expanded in peripheral blood lymphocytes (PBL) from patients with human papilloma virus (HPV)+ cervical lesions as well as in PBL from patients with pulmonary tuberculosis. Flow-cytometric cell sorted CD8+ CD45RA+ CD28- and CD8+ CD45RA+ CD28- T cells were tested for recognition of HLA-A2 restricted peptides derived either from the human papillomavirus (HPV)16-E7 gene product, or from M. tuberculosis antigens. Mostly CD8+ CD45+ CD28- T cells define antigen/peptide-specific and MHC-restricted responses. These data were confirmed in PBL from patients with tuberculosis using HLA-A2 tetramer-complexes loaded with a peptide from the M. tuberculosis Ag85b antigen by flow cytometry. The sorting of this T cell subset enables to determine the fine specificity of CD8+ effector T cells without the need for in vitro manipulation. 相似文献
7.
K. Steiner F. Moosig E. Csernok K. Selleng W. L. Gross B. Fleischer B. M. Brker 《Clinical and experimental immunology》2001,126(1):143-150
CTLA-4 (CD152) is a surface molecule of activated T cells with sequence homology to CD28. Both molecules bind to the same ligands, B7.1 (CD80) and B7.2 (CD86) but have antagonistic functions. While CD28 is an important costimulator, CTLA-4 has an essential inhibitory function in maintaining the homeostasis of the immune system. Furthermore, CTLA-4 has a role in inducing a Th1 response and suppressing Th2 cytokines, an effect which is antagonized by CD28. Many autoimmune diseases are characterized by an overwhelming production of Th1 cytokines. Recently, the predominance of the Th1 cytokine pattern has been directly observed in the granulomatous inflammation of patients with Wegener's granulomatosis. The balance between CD28 and CTLA-4 expression by T lymphocytes could be a factor in the pathogenesis of autoimmune diseases. Down regulation of CD28 predominantly on CD8+ T cells has been described in Wegner's granulomatosis; however, analysis of CTLA-4 is complicated by its low expression levels. Here we have used potent signal enhancement to study CTLA-4 on PBMC in patients with Wegener's granulomatosis (n = 25) in comparison with healthy controls (n = 19). Expression levels of CTLA-4 were significantly increased selectively on CD4+ and possibly also on CD4-/CD8- T cells in Wegener's granulomatosis. High CTLA-4 expression by T lymphocytes was associated with more severe disease. In contrast, after stimulation with the mitogen PHA, CTLA-4 levels were strongly increased on T cells from controls but in T cells from Wegener's granulomatosis patients this response was severely impaired. Interestingly, while CTLA-4 was seen exclusively on T cells in control individuals, about half of the Wegener's patients showed CTLA-4 expression by a fraction of peripheral B lymphocytes. CTLA-4 positive B cells in the periphery were associated with less acute disease. 相似文献
8.
Karabon L Pawlak E Tomkiewicz A Jedynak A Passowicz-Muszynska E Zajda K Jonkisz A Jankowska R Krzakowski M Frydecka I 《Human immunology》2011,72(10):947-954
Polymorphisms in genes encoding CD28, ICOS, and CTLA-4 were demonstrated to be associated with susceptibility to malignancies. To the best of our knowledge, no study on this association has been performed in a Caucasian population for non-small-cell lung cancer (NSCLC). In the present work, we investigated the polymorphisms CTLA-4c.49A>G (rs231775), CTLA-4g.319C>T (rs5742909), CTLA-4g.*642AT(8_33), CTLA-4g.*6230G>A (CT60) (rs3087243), CTLA-4g.*10223G>T (Jo31) (rs11571302), CD28c.17+3T>C (rs3116496), and ICOSc.1554+4GT(8_15) in 208 NSCLC patients and 326 controls. The distributions of the allele and genotype were similar in both groups for CTLA-4, CD28, and ICOS gene polymorphisms. However, we noted a tendency toward overrepresentation of individuals possessing the CTLA-4c.49A>G[A] allele in NSCLC patients compared with controls (0.84 vs 0.79, p = 0.09). The association became significant compared with controls in women for the CTLA-4c.49A>G[A] allele and CTLA-4c.49A>G[AA] genotype (0.67 vs 0.54, p = 0.01, and 0.47 vs 0.30, p = 0.02; respectively). Moreover, the constellation of alleles CTLA-4c.49A>G[A]/CT60[G]/CD28c.17+3T>C[T]/ICOSc.1554+4GT(8_15)[>10] increased the risk of NSCLC about 2-fold (p = 0.002). The same constellation of alleles combined with smoking, CTLA-4g.319C>T[T], and ICOSc.1554+4GT(8_15)[>10] was associated with a decreased overall survival rate. In conclusion, the constellation of specific alleles in CTLA-4, CD28, and ICOS genes contributes to the susceptibility and clinical course of NSCLC. 相似文献
9.
Kenneth Williams Elling Ulvestad Jack P. Antel 《European journal of immunology》1994,24(12):3031-3037
In this study, we have examined the expression and function of B7/BB-1 on individual glial cells, by utilizing surgically resected adult human central nervous system (CNS) tissues, tissues derived from fetal human CNS, and pathology material from cases of multiple sclerosis (MS). Immunofluorescence analysis using enriched adult human derived cultures of microglia and oligodendrocytes, and mixed microglia/astrocyte cultures, demonstrated that B7/BB-1 was expressed on microglia. Adult human-derived oligodendrocytes and astrocytes, and human fetal astrocytes were B7/BB-1 negative under all culture conditions. Flow cytometry studies demonstrated a low basal level of B7/BB-1 expression on microglia that was up-regulated following incubation with interferon-γ (IFN-γ). Co-culture of purified fresh allogeneic CD4+ T cells with microglia for 24 h resulted in clustering of T cells around microglia and microglial B7/BB-1 expression. Preincubation of microglia with an anti BB-1 monoclonal antibody (mAb) prior to microglia: CD4+ T cell co-cultures resulted in partial inhibition of the ability of microglia both to present recall antigen to autologous CD4+ T cells and to present antigen to allogeneic CD4+ T cells in primary mixed lymphocyte reaction (1°MLR). The CTLA-4 Ig fusion protein inhibited the ability of microglia to present antigen in both antigen presentation assays to an even greater extent than did the anti BB-1 mAb. The BB-1 antibody also inhibited the ability of microglia to stimulate previously activated T cells in a secondary 2° MLR. In sections of multiple sclerosis brain, B7/BB-1 expression was observed on activated microglia in select parenchymal lesions, and on perivascular cells and infiltrating monocytes. B7/BB-1 immunoreactivity was not found in normal appearing white matter from MS brain or from non-inflammatory brain specimens. Our results indicate that the B7/BB-1 molecule plays a functional role in the capacity of microglia to serve as CNS antigen-presenting cells that can both initiate and perpetuate CD4+ T cell activation. 相似文献
10.
Monoclonal antibodies reactive for B cells, T cells, T-cell subsets, killer (K) and natural killer (NK) cells, and the Ia antigen were used to analyze mononuclear cell subsets in scleroderma (SD), dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM), Duchenne dystrophy (DD), and normal muscle. The analysis, which was quantitative, was performed according to diagnosis and site of accumulation. Cells at perivascular, perimysial, and endomysial sites of accumulation, and cells focally surrounding and invading nonnecrotic muscle fibers, were analyzed separately. Individual antigens were localized in 2-micron serial sections, or multiple antigens were demonstrated in a given section by sequential paired immunofluorescence. The latter approach allowed the identification of the cell phenotypes in which functional properties are defined by multiple markers, e.g., T8+ and T4+ cells that are either activated or not activated, T8+ cells that are either cytotoxic or suppressor T cells, and K/NK cells of varying maturity and killing capability. The interactions of inflammatory cells of various types with each other and the muscle fiber were further investigated by immunoelectron microscopy. In SD, the findings provide evidence for a cell-mediated immune effector response against a connective tissue and/or vascular element. In DM, the effector response appears to be predominantly humoral. In PM and IBM (but not in DM or SD), there is invasion and destruction of nonnecrotic muscle fibers by cytotoxic T cells, with or without accompanying macrophages. Because T-cell-mediated injury is antigen- and major histocompatibility complex-restricted, clones of T cells must have been sensitized previously to a muscle fiber-associated surface antigen. The identity of the putative antigen(s) remains an important, unsolved question. 相似文献
11.
Inhibition of CD40 signaling pathway in antigen presenting cells by T suppressor cells. 总被引:5,自引:0,他引:5
Understanding the mechanism which underlies the induction of immunologic tolerance is crucial to the development of strategies for treatment of autoimmune diseases and allograft rejection. Although the concept that T suppressor cells (Ts) downregulate the immune response has long been accepted, the existence of a distinct population of lymphocytes that mediates suppression has not been convincingly demonstrated. In previous studies, we have utilized human T cell lines (TCLs) to analyze the suppressive effects of CD8+CD28 T cells in allogeneic, peptide specific and xeno-specific responses. In each case, CD8+CD28- T cells inhibit proliferation of CD4+ T helper lymphocytes (Th) with cognate antigen specificity. These CD8+CD28- T cells display the critical functional characteristics of T suppressor cells. Similar to the induction of CD8+ cytotoxic T cells (Tc) by Th, this process depends on antigen presenting cells (APC) acting as a "bridge" between MHC-class I specific CD8+ and class II specific CD4+ T cells. A possible explanation of Ts-mediated suppression is their ability to modulate the function of APCs. The present studies show that CD8+CD28- Ts directly inhibit the CD40 signaling pathway of APC by a contact-dependent mechanism that renders bridging APCs incapable of inducing CD4+ Th activation. The effects of Ts on the functional state of APC supports the concept that the order in which Ts and Th cells interact with cognate APCs determines the functional outcome of immune responses. 相似文献
12.
1.用羊抗鼠IgG(20μg/ml)包被96孔细胞培养板,再加入游离的激发型CD28单抗(终浓度为5 μg/ml);2.用激发型CD28单抗(10 μg/ml)直接包被96孔细胞培养板,然后分别加入10~5个/孔经E-花结实验获取的人外周血T细胞(PBTC),其中CD3+T>95%。逐日观察细胞的生长状态并绘制生长曲线,用3H-TdR掺入法分析PBTC的增殖效应,用FITC标记的单抗经流式细胞仪(FCM)分析细胞CD3、CD4、CD8、CTLA-4、4-1BB及OX40的表达。逐日细胞计数的结果表明,经羊抗鼠IgG包被后加入游离激发型CD28单抗或直接用激发型CD28单抗包被,均能引发PBTC的活化与增殖效应,激发3 d时的刺激指数(SI)大于9,细胞CD3、CD4、CD8、CTLA-4、4-1BB及OX40的阳性表达率(x±s,%)分别为98.6±0.2、74.4±3.1、22.5±2.0、2.1±0.4、18.4±2.2、35.2±3.5。与XGB7(作为APC)刺激的T细胞相比,经CD28单抗直接激发的T细胞,CD4+/CD8+T细胞的比值及OX40+T细胞的百分率升高(P<0.01),但不表达负性调节分子CTLA-4。 相似文献
13.
14.
CD69, HLA-DR and the IL-2R identify persistently activated T cells in psoriasis vulgaris lesional skin: blood and skin comparisons by flow cytometry 总被引:24,自引:0,他引:24
Many lymphocyte-activation-associated molecules are observed by immunohistochemistry in psoriasis vulgaris lesional skin. Non-T cells in lesional skin also express these molecules. We quantitatively measured the number of T cells expressing cell surface activation-associated molecules (CD69, CD25, CD122, HLA-DR) and co-stimulatory molecules (CD28, CTLA-4, CD80, CD86), including a Type 2 T cell marker (CD30) and CD11b, by flow cytometry of skin and peripheral blood. T cells in single cell suspensions of psoriatic lesional-epidermis-expressed HLA-DR (86%), CD69 (59%), CD25 (55%), CD122 (44%), and CD28 (91%). Dermal T cells showed similar percentages except for CD69 (17%). CD69 was found directly in lesional skin biopsies by immunohistochemistry. Both CD4 and CD8 subsets from lesional skin contained large populations of CD25+ cells with a bias towards CD8 activation in the epidermis and towards CD4 activation in the dermis. CD86, CD80, CTLA-4, CD30 and CD11b were expressed by less than 23% of the T cell populations from both the epidermis and dermis. CD30+CD4+ cells were found two-fold over CD8+ T cells. These results show that the majority of lesional lymphocytes are persistently activated. We also found the majority of Type 2 associated markers primarily on the CD4+ epidermal T cell population. Psoriatic blood contained elevated levels of T cells expressing CD25, primarily within the CD8+ subset. Thus the majority of lesional T cells expressed the three primary activation markers, while psoriatic blood T cells were distinguished by an increase in CD25, specifically within the CTL population. 相似文献
15.
Overlap between molecular markers expressed by naturally occurring CD4+CD25+ regulatory T cells and antigen specific CD4+CD25+ and CD8+CD28- T suppressor cells 总被引:12,自引:0,他引:12
Scotto L Naiyer AJ Galluzzo S Rossi P Manavalan JS Kim-Schulze S Fang J Favera RD Cortesini R Suciu-Foca N 《Human immunology》2004,65(11):1297-1306
Alloantigen specific CD8+CD28- T suppressor (TS) cells differ from naturally occurring CD4+CD25+ T-regulatory (natural TR) cells not only by their phenotype but also by their mechanism of action. Natural TR have been extensively studied, leading to the identification of characteristic "molecular markers" such as Forkhead box P3 (FOXP3), glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). We have investigated the expression of these genes in alloantigen specific TS and CD4+CD25+ T regulatory (TR) cells and found that they are expressed at levels similar to those observed in natural TR. Furthermore, similar to natural CD4+CD25+ TR, antigen-specific CD8+CD28-CD62L+ TS cells have more suppressive capacity than CD8+CD28-CD62L- TS cells. In spite of these similarities, natural TR are not antigen-specific and inhibit other T cells by T cell-to-T cell interaction, whereas TS are antigen-specific and exert their inhibitory function by interacting with antigen-presenting cells and render them tolerogenic to other T cells. The molecular characterization of TS cells may contribute to a better understanding of mechanisms involved in inhibition of immune responses in autoimmunity, transplantation, and chronic viral infection. 相似文献
16.
17.
目的 对中国HIV感染者T细胞及凋节性T细胞CTLA-4表达与HIV疾病进展的相关性进行研究,探讨CTLA-4在HIV感染中的作用.方法 选取58名HIV/AIDS患者(长期不进展组、无症状HIV组、AIDS组),应用流式细胞仪胞内染色技术检测T细胞及CD4+CD25+Foxp3+调节性T细胞内CTLA-4表达水平,分析其与CD4+T细胞、病毒载量、淋巴细胞活化凋亡水平的相关性.结果 长期不进展组、无症状HIV组、AIDS组CD4+T细胞内CTLA-4表达水平依次增岛(P<0.05);与CD+T细胞显著负相关(P<0.01),与CD8+T细胞活化(CD38表达)、凋亡水平(CD95表达)及CD4+T细胞凋亡水平显著相关(P<0.05),与病毒载量无显著相关性.长期不进展组、无症状HIV组、AIDS组CD8+T细胞内CTLA-4表达水平差异无统计学意义;与CD4+T细胞、病毒载量、CD4,'+>、CD8+T细胞活化及凋亡水平均无显著相关性.CD4+CD25+Foxp3+T细胞内CTLA-4表达水平长期不进展组明显低于无症状HIV组及AIDS纽(P<0.05);与CD4+T细胞显著负相关(P<0.05);与CD4+、CD8+T淋巴细胞活化(HLA-DR表达)显著相关(P<0.01).结论 中国HIV感染者CD4+T细胞及CD4+CD25+Foxp3+调节性T细胞内CTLA-4表达水平与疾病进展及免疫活化状态显著相关,参与HIV感染免疫平衡的调节. 相似文献
18.
Immunocytochemical study of CD45 T cell isoforms in inflammatory myopathies. 总被引:1,自引:0,他引:1
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The CD45RO and CD45RA antigens subdivide the CD8+ and the CD4+ T cells into primed memory cells and unprimed virgin T cells, respectively. To assess the relative abundance of the CD8+ and the CD4+ T cells expressing the two CD45 isoforms in the major inflammatory myopathies, we immunophenotyped T cells in muscle specimens from patients with inclusion body myositis, polymyositis (PM), and dermatomyositis. The analysis was according to diagnosis and sites of cell accumulation: endomysial inflammatory cells focally surrounding and invading nonnecrotic fibers were analyzed in inclusion body myositis and PM and perivascular infiltrates in PM and dermatomyositis. In all diseases and at all sites of accumulation, the CD45RO+ memory T cells were predominant and the CD45RO/CD45RA ratio exceeded that in normal blood. In PM and inclusion body myositis, the marked enrichment of endomysial T cells in memory cells implicates these cells in the pathogenesis. The enrichment of perivascular T cells in dermatomyositis and PM in memory cells may be a result of enhanced transendothelial migratory capacity of these cells; alternatively, the virgin-to-memory cell conversion may occur after diapedesis. 相似文献
19.
Accumulation of CTLA-4 expressing T lymphocytes in the germinal centres of human lymphoid tissues. 总被引:1,自引:0,他引:1
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CTLA-4, a coreceptor with sequence homology to CD28 is expressed on T cells after activation. Mice deficient for CTLA-4 die young from massive infiltration of many organs by activated T cells, which highlights the essential inhibitory role the coreceptor plays in the regulation of the immune response. To study the prevalence and distribution of CTLA-4 in situ immunohistological analyses were carried out on human tonsils and lymph nodes. Expression of CTLA-4 was restricted to alpha beta T cells, and CTLA-4+ B cells were not observed. In T-cell areas, 2-10% of T cells were positive for CTLA-4 with similar percentages in the CD4+ and CD8+ subpopulations. In the germinal centres (GC) the fraction of CTLA-4+ T cells was much higher (70-90%). This was due to frequent expression of CTLA-4 on the CD4+ helper subpopulation. GC CD8+ T cells were rare and mostly did not express the coreceptor. The CTLA-4+ T-cell fraction was also over-represented among intraepithelial tonsillar T cells. Cycling (Ki-67+) and apoptotic (TUNEL+) T cells were never positive for CTLA-4, while a subset of CD25+ cells did express the coreceptor. Since CTLA-4 is essential for the physiological limitation of the immune response, GC T cells, which are mostly CTLA-4 positive, might be important in this process. 相似文献
20.
Discordant expression of CD28 ligands, BB-1, and B7 on keratinocytes in vitro and psoriatic cells in vivo. 总被引:8,自引:4,他引:8
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B. J. Nickoloff R. S. Mitra K. Lee L. A. Turka J. Green C. Thompson Y. Shimizu 《The American journal of pathology》1993,142(4):1029-1040
The process for optimal T-cell activation requires not only engagement of the T-cell receptor/CD3 complex, but also the delivery of additional co-stimulatory signals that synergize with the primary response mediated through the T-cell receptor. Thus, the regulated expression of ligands for such co-stimulatory molecules can be critical in determining whether a cell can effectively activate T cells following the presentation of a foreign antigen. The CD28 antigen has recently been shown to mediate such co-stimulatory signals by interacting with the B7/BB-1 molecule expressed on activated B cells and monocytes. We show in this study that activated keratinocytes, both in vitro and in vivo display a discordance in expression between B7 and BB-1 based on differential monoclonal antibody (MAb) reactivity. Activated keratinocytes in vitro, as well as psoriatic keratinocytes and epithelial cells in the thymus, are reactive with the BB-1 MAb but not anti-B7 MAbs. These BB-1 positive cells fail to express detectable B7 messenger RNA by Northern blot analysis. Furthermore, keratinocytes bind specifically to CD28-transfected COS7 cells, and this binding is inhibited by anti-CD28 and anti-BB-1 but not B7 MAbs. These studies suggest: 1) that the MAb against BB-1 binds a functional epitope on a molecule distinct from B7 as detected on activated keratinocytes in vitro and in vivo and 2) that keratinocytes in skin and epithelial cells in thymus can express cell-surface molecules that might mediate T-cell co-stimulation via CD28. 相似文献