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1.
Characterization of porcine T lymphocytes and their immune response against viral antigens. 总被引:5,自引:0,他引:5
T lymphocytes play a central role in the antigen-specific immune response against various pathogens. To detect and to characterize porcine T lymphocytes, monoclonal antibodies (mAb) against leukocyte differentiation antigens had been raised and classified for their specificity. Analyses of porcine T lymphocytes with specific mAb against CD4 and CD8 differentiation antigens revealed differences in the composition of the porcine T-lymphocyte population compared to other species. In addition to the known subpopulations, CD4+CD8- T helper cells and CD4-CD8+ cytolytic T lymphocytes, extra-thymic CD4+CD8+ T lymphocytes and a substantial proportion of CD2-CD4-CD8- T cell receptor (TcR)-gamma delta+ T cells could be detected in swine. Functional analyses of porcine T-lymphocyte subpopulations revealed the existence of two T-helper cell fractions with the phenotype CD4+CD8- and CD4+CD8+. Both were reactive in primary immune responses in vitro, whereas only cells derived from the CD4+CD8+ T-helper-cell subpopulation were able to respond to recall antigen in a secondary immune response. With regard to T lymphocytes with cytolytic activities, two subsets within the CD4-CD8+ T-cell subpopulation could be defined by the expression of CD6 differentiation antigens: CD6- cells which showed spontaneous cytolytic activity and CD6+ MHC I-restricted cytolytic T lymphocytes including virus-specific cytolytic T lymphocytes. These results enable now a detailed view into the porcine T-cell population and the reactivity of specific T cells involved in the porcine immune response against pathogens. Furthermore this knowledge offers the possibility to investigate specific interactions of porcine T lymphocytes with virus-specific epitopes during vaccination and viral infections. 相似文献
2.
The peripheral blood distribution of T cell subsets was evaluated in a group of patients with primary IgA nephropathy (IgAN). Results showed that the frequency of helper (CD4+) and suppressor (CD8+) T lymphocytes in IgAN overlapped that seen in healthy blood donors. In addition, the helper T cell subset (CD4+ CDW29+ and CD4+ CD45R+ cells, respectively) proportion was normal, while with particular reference to suppressor T cell subpopulations, a significant decrease of CD8+ CD11+ lymphocytes (the true suppressor cells) was observed in IgAN. These data were further confirmed by the demonstration that monocyte chemotactic responsiveness triggered by lymphocyte-derived chemotactic factor (LDCF), a lymphokine released by CD8+ CD11- cells, was higher in IgAN than in controls. These data suggest that the low frequency of CD8+ CD11+ cells may be responsible for the impaired T cell immunoregulatory activity in patients with IgAN. 相似文献
3.
Bovine and human insulin activate CD8+-autoreactive CTL expressing both type 1 and type 2 cytokines in C57BL/6 mice 总被引:2,自引:0,他引:2
CD8+ T cells down-regulate a variety of immune responses. For example, porcine and human insulin do not stimulate Abs in C57BL/6 mice because CD8+ T cells inhibit CD4+ helper T cells. By contrast, bovine insulin induces Ab in C57BL/6 mice, and removal of CD8+ T cells does not alter this response. This raises the question of whether porcine, but not bovine, insulin activates CD8+ T cells or whether both insulins activate CD8+ T cells but CD4+ helper T cells are differentially inhibited by them. In this study, we show that insulin-specific CD8+ CTL can be cultured from C57BL/6 mice primed with either bovine or human insulin in CFA. Thus, exogenous Ags, besides OVA, induce CD8+ CTL when administered in an adjuvant, suggesting this is a typical response. These CTL are H-2Kb restricted and produce IL-5, IL-10, IFN-gamma, and small amounts of IL-4, which is distinct from IFN-gamma and TNF-alpha that are typically secreted by virus-specific CTL. Moreover, the CTL primed with either bovine or human insulin recognize an A-chain peptide that is identical to the mouse insulin sequence. That foreign proteins, which are closely related to self-proteins, activated autoreactive, CD8+ T cells in vivo is a novel finding. It raises the possibility that self-reactive CTL may be activated by cross-reacting Ags and once activated they might participate in autoimmunity. These results also suggest that down-regulation of insulin-specific responses by autoreactive CD8+ T cells is most likely due to the differential sensitivity of bovine and human insulin-specific CD4+ T cells. 相似文献
4.
Sawicka E Dubois G Jarai G Edwards M Thomas M Nicholls A Albert R Newson C Brinkmann V Walker C 《Journal of immunology (Baltimore, Md. : 1950)》2005,175(12):7973-7980
The sphingosine 1-phosphate (S1P) receptor agonist FTY720 is well known for its immunomodulatory activity, sequestering lymphocytes from blood and spleen into secondary lymphoid organs and thereby preventing their migration to sites of inflammation. Because inflammation is critically dependent on a balance between Ag-specific Th/effector cells and T-regulatory cells, we investigated the effect of FTY720 on T-regulatory cell trafficking and functional activity. An increased number of CD4+/CD25+ T cells was found in blood and spleens of FTY720-treated mice, and transfer of these cells resulted in a significantly more pronounced accumulation in spleens but not lymph nodes after treatment, suggesting that this compound differentially affects the homing properties of T-regulatory cells compared with other T cell subsets. Indeed, CD4+/CD25+ T cells express lower levels of S1P1 and S1P4 receptors and demonstrate a reduced chemotactic response to S1P. Moreover, analysis of the functional response of FTY720-treated CD4+/CD25+ T cells revealed an increased suppressive activity in an in vitro Ag-specific proliferation assay. This correlated with enhanced function in vivo, with T-regulatory cells obtained from FTY720-treated mice being able to suppress OVA-induced airway inflammation. Thus, FTY720 differentially affects the sequestration of T-regulatory cells and importantly, increases the functional activity of T-regulatory cells, suggesting that it may have disease-modifying potential in inflammatory disorders. 相似文献
5.
The majority of human peripheral blood CD4+CD25highFoxp3+ regulatory T cells bear functional skin-homing receptors 总被引:7,自引:0,他引:7
Hirahara K Liu L Clark RA Yamanaka K Fuhlbrigge RC Kupper TS 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(7):4488-4494
CD4+CD25+ T regulatory cells (Treg) are thought to be important in the peripheral tolerance. Recent evidence suggests that human peripheral blood CD4+CD25+ T cells are heterogeneous and contain both CD4+CD25(high) T cells with potent regulatory activity and many more CD4+CD25(low/med) nonregulatory T cells. In this study, we found that virtually all peripheral blood CD4+CD25(high)Foxp3+ Treg expressed high levels of the chemokine receptor CCR4. In addition, 80% of Treg expressed cutaneous lymphocyte Ag (CLA) and 73% expressed CCR6. These molecules were functional, as CLA+ Treg showed CD62E ligand activity and demonstrable chemotactic responses to the CCR4 ligands CCL22 and CCL17 and to the CCR6 ligand CCL20. The phenotype and chemotactic response of these Treg were significantly different from those of CD4+CD25(med) nonregulatory T cells. We further demonstrated that blood CLA+ Treg inhibited CD4+CD25- T cell proliferation induced by anti-CD3. Based on homing receptor profile, CLA+ Treg should enter normal skin. We next isolated CD4+CD25(high) T cells directly from normal human skin; these cells suppressed proliferation of skin CD4+CD25- T cells. Therefore, the majority of true circulating Treg express functional skin-homing receptors, and human Treg may regulate local immune responses in normal human skin. 相似文献
6.
Human CD4+ T cells mediate rejection of porcine xenografts 总被引:4,自引:0,他引:4
Friedman T Shimizu A Smith RN Colvin RB Seebach JD Sachs DH Iacomini J 《Journal of immunology (Baltimore, Md. : 1950)》1999,162(9):5256-5262
It has previously been demonstrated that xenograft rejection in rodents is dependent on CD4+ T cells. However, because of the lack of an appropriate in vivo model, little is known about the cellular basis of human T cell-mediated rejection of xenografts. In this study, we have evaluated the ability of human T cells to mediate rejection of porcine skin grafts in a novel in vivo experimental system using immunodeficient mice as recipients. Recombinase-activating gene-1-deficient mice (R-) lacking mature B and T cells were grafted with porcine skin and received human lymphocytes stimulated in vitro with irradiated porcine PBMC. Skin grafts on mice given either unseparated, activated human lymphocytes, or NK cell-depleted lymphocyte populations were rejected within 18 days after adoptive cell transfer. In contrast, skin grafts on mice given T cell-depleted human lymphocytes or saline showed no gross or histologic evidence of rejection up to 100 days after adoptive transfer. Purified CD4+ T cells were also able to mediate rejection of porcine skin grafts. These data suggest that human CD4+ T cells are sufficient to induce rejection of porcine xenografts. Thus, strategies directed toward CD4+ T cells may effectively prevent cellular rejection of porcine xenografts in humans. 相似文献
7.
J A Marsh B E Johnson H S Lillehoj C G Scanes 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1992,199(1):114-122
The effect of thyroxine (T4) and/or recombinant chicken growth hormone (rcGH) supplementation on immune function and on immune cell maturation was examined in Obese strain chickens. Day-old Obese strain chicks received the control treatments or were treated with either T4 (supplemented in the diet), T4-rcGH, or rcGH (by daily injection) in a full factorial design. At 4 weeks of age, the proliferative activity of peripheral blood T cells to either mitogenic or allogenic cell (mixed lymphocyte response) challenge was assessed. At the same time, peripheral blood lymphocytes and thymocytes were collected and prepared for flow cytometry analysis. Proliferative responses to both T cell mitogens and allogeneic splenocytes were significantly increased (P less than 0.05) by rcGH treatment, while the combined T4-rcGH treatment resulted in a significant increase in allogeneic and in concanavalin A responsiveness, but not in the response to phytohemagglutinin. All supplemented groups showed a significant decrease in the mean fluorescent intensity for CT-1a+ thymocytes, while thymocytes from birds receiving either T4 or rcGH alone had higher proportions of CD4+ and CD8+ cells. The monoclonal antibody staining of thymocytes from T4-rcGH-supplemented animals more closely resembled that of the unsupplemented controls. Among the peripheral blood lymphocytes, there were no changes in the numbers of CD4+, CD8+, or sIg+ cells as a result of treatment. The mean fluorescent intensity of sIg+ cells was significantly decreased, however, as a result of T4 supplementation when given either alone or in combination with rcGH. Finally, the mean fluorescent intensity ratios of CD4+ to CD8+ cells was significantly increased as a result of rcGH supplementation. These results strongly support a role for both the thyroid hormones and growth hormone in regulating and/or enhancing immune function, with changes in functional responses paralleled by concomitant changes in the T cell populations as expressed by shifts in T cell surface marker expression. 相似文献
8.
Hansenne I Renard-Charlet C Greimers R Geenen V 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(8):4651-4657
There is some evidence that insulin-like growth factor 2 (IGF-2) may intervene in the control of T cell differentiation. To further study the immunoregulatory function of this growth factor, we analyzed the immune system of Igf2-/- mice. Phenotypically, some immunological parameters such as lymphoid organ morphology and cellularity were unaltered in Igf2-/- mice, but an increase of CD8+ cells and a decrease of B220+ cells were observed in spleen. In vitro, the development of bone marrow-derived dendritic cells was affected by the absence of Igf2 expression. After maturation, a higher percentage of immature dendritic cells was observed in Igf2-/- population, together with a secondary decrease in allogenic T cell proliferation. Activation of T cells was also affected by the lack of expression of this growth factor. The profile of B cell response in mutant mice immunized with IGF-2 evidenced a T-dependent profile of anti-IGF-2 Abs that was absent in Igf2+/+ mice. The influence of IGF-2 upon tolerance to insulin was also assessed in this model, and this showed that IGF-2 also intervenes in tolerance to insulin. The presence of a T-dependent response in Igf2-deficient mice should allow cloning of specific "forbidden" T CD4+ lymphocytes directed against IGF-2, as well as further investigation of their possible pathogenic properties against insulin family. 相似文献
9.
Vaughan AN Malde P Rogers NJ Jackson IM Lechler RI Dorling A 《Journal of immunology (Baltimore, Md. : 1950)》2000,165(6):3175-3181
The CTLA4 receptor (CD152) on activated T lymphocytes binds B7 molecules (CD80 and CD86) on APC and delivers a signal that inhibits T cell proliferation. Several regions involved in binding to B7 are known, but the relative importance of these is not clear. We have cloned porcine CTLA4 (pCTLA4). Although highly homologous to human CTLA4 (hCTLA4), the predicted protein sequence contains a leucine for methionine substitution at position 97 in the MYPPPY sequence. A fusion protein constructed from the extracellular regions of pCTLA4 and the constant regions of human IgG1 (pCTLA4-Ig) bound porcine CD86 with equivalent affinity to that of hCTLA4-Ig. However, pCTLA4-Ig bound poorly to human CD80 and CD86 expressed on transfectants and EBV-transformed human B cells. In functional assays with MHC class II-expressing porcine endothelial cells and human B cells, pCTLA4-Ig blocked human CD4+ T cell responses to pig but not human cells, whereas control hCTLA4-Ig inhibited responses to both. Comparison between mouse, human, and porcine CTLA4-Ig suggests that the selective binding of pCTLA4-Ig to porcine CD86 molecules is due to the L for M substitution at position 97. Our results indicate that pCTLA4-Ig may be a useful reagent to define the precise nature of the interaction between B7 and CTLA4. By failing to inhibit the delivery of costimulatory signals provided by human B7, it may also prove to be a relatively specific inhibitor of the direct human T cell response to immunogenic pig tissue. 相似文献
10.
L. Govan 《Cytopathology》2006,17(Z1):23-23
Introduction: Despite the cervix having the largest concentration of lymphocytes and macrophages in the lower genital tract, there is limited knowledge of these cell types in CIN. This study was undertaken to compare T‐cell and macrophage populations in women with and without low‐grade CIN. Methods: Control group: 10 women with a normal recent cervical smear result, mean age 30 years. Study group: 10 women with low‐grade CIN, mean age 33.2 years. Colposcopically directed cervical biopsies were taken from control women and from areas of CIN in the study group, and studied using immunoperoxidase and immunofluorescence staining. Results: T‐cell numbers remained constant. In CIN, there were increased proportions of recruited (CD8+CD5+), activated (CD8+HLA‐DR+) and cytolytic (CD8+TIA‐1+) CD8 T‐cells. There were more activated CD4+HLA‐DR+ T‐cells in CIN. Memory T‐cell (CD8+CD45RO+ and CD4+CD45RO+) proportions were reduced. Total macrophage numbers (CD68+) remained constant, but activated macrophages (CD68+HLA‐DR+) rose. Phagocytic (RFD7+) macrophage proportions decreased with a concomitant increase in suppresser macrophages (RFD1+RFD7+). Discussion: Despite cellular numbers remaining unchanged, there were significant changes in T‐cell and macrophage populations in women with low‐grade CIN. There is recruitment of activated and cytolytic CD8 T‐cells. The swing to a predominantly suppressive macrophage phenotype may predispose to CIN. Carcinoma of the cervix occurs more frequently in women who are immunosuppressed. Our data suggests that local and systemic immune mechanisms may be relevant in the response to HPV‐induced neoplasia. 相似文献
11.
The accumulation of mononuclear cells at sites of chronic inflammation is dependent on a number of factors including localized adherence of lymphocytes to vascular endothelial cells (EC), cytokine-mediated increased adhesiveness of endothelium, chemotactic factors and endothelial permeability. The present study investigates two of the above attributes of lymphocyte-EC interaction: namely, the ability of maturationally distinct subpopulations of human T lymphocytes to adhere to vascular EC and to increase vascular endothelial permeability to macromolecules in an in vitro model. Thus, human T lymphocytes were separated into CD4+ CD8-helper/inducer, CD4- CD8+ cytotoxic/suppressor, CD29+ CD45RA- CD45RO+ memory, and CD29- CD45RA+ CD45RO- naive/virgin T subpopulations, were activated with PHA and PMA, and then examined for their adherence to EC and also for their effect on endothelial permeability. Upon activation, cells within each of the above four subpopulations exhibited increased adherence to EC. In contrast, resting CD29+ CD45RA- CD45RO+ memory T lymphocytes exhibited two to three times greater ability to adhere to EC than their CD29- CD45RA+ CD45RO- naive/virgin counterparts. Consistent with their increased adherence to EC, CD29+ CD45RO+ memory T lymphocytes, when activated, significantly increased endothelial permeability to albumin. Although activated CD45RA+ naive T lymphocytes exhibited increased adherence to EC, these cells failed to increase significantly endothelial permeability. Similar to their polyclonal counterparts, Ag-specific CD4+ CD29+ CD45RO+ T cell clones, but not their actively released mediators, also increased endothelial permeability via a noncytolytic mechanism(s). This ability of CD29+ CD45RO+ memory T lymphocytes to augment endothelial permeability may facilitate their transendothelial migration into extravascular space. These observations may provide additional insights into molecular mechanism(s) underlying pathophysiology of localized chronic inflammatory responses in general and more specifically selective accumulation of CD29+/CD45RO+ memory T lymphocytes at sites of chronic inflammation such as rheumatoid synovium. 相似文献
12.
Primary CD4+ T-cell responses provide both helper and cytotoxic functions during Epstein-Barr virus infection and transformation of fetal cord blood B cells
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Most humans carry Epstein-Barr virus (EBV) in circulating memory B cells as a latent infection that is controlled by an immune response. When infected by EBV, B lymphocytes in fetal cord blood are readily transformed to lymphoblastoid cell lines (LCL). It is frequently assumed that this high efficiency of transformation is due to the absence of a primary immune response. However, cord blood lymphocytes stimulated with autologous LCL yield CD4+ T cells that can completely inhibit the growth of LCL by a major histocompatibility complex-restricted cytotoxic mechanism mediated by granulysin and granzyme B. Because EBV-transformed B cells maintain the phenotype of antigen-activated B-cell blasts, they can potentially receive inhibitory or helper functions from CD4+ T cells. To assess these functions, the effect of EBV-specific CD4+ T cells on the efficiency of virus transformation of autologous B cells was assayed. Paradoxically, although the cytotoxic CD4+ T-cell lines reduced EBV B-cell transformation at a high effector/target ratio of 10:1, they caused a twofold increase in B-cell transformation at the lower effector/target ratio of 1:1. Th1-polarized CD4+ T cells were more effective at inhibiting B-cell transformation, but Th2-polarized cell lines had reduced cytotoxic activity, were unable to inhibit LCL growth, and caused a 10-fold increase in transformation efficiency. Tonsil lymphoid follicles lacked NK cells and CD8+ T cells but contained CD4+ T cells. We propose that CD4+ T cells provide helper or cytotoxic functions to EBV-transformed B cells and that the balance of these functions within tonsil compartments is critical in establishing asymptomatic primary EBV infection and maintaining a stable lifelong latent infection. 相似文献
13.
14.
Oh HL Chia A Chang CX Leong HN Ling KL Grotenbreg GM Gehring AJ Tan YJ Bertoletti A 《Journal of virology》2011,85(20):10464-10471
Severe acute respiratory syndrome (SARS) is a highly contagious and life threatening disease, with a fatality rate of almost 10%. The etiologic agent is a novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV), with animal reservoirs found in bats and other wild animals and thus the possibility of reemergence. In this study, we first investigated at 6 years postinfection whether SARS-specific memory T cells persist in SARS-recovered individuals, demonstrating that these subjects still possess polyfunctional SARS-specific memory CD4+ and CD8+ T cells. A dominant memory CD8+ T cell response against SARS-CoV nucleocaspid protein (NP; amino acids 216 to 225) was then defined in SARS-recovered individuals carrying HLA-B*40:01, a HLA-B molecule present in approximately one-quarter of subjects of Asian ethnicities. To reconstitute such a CD8+ T cell response, we isolated the alpha and beta T cell receptors of the HLA-B*40:01-restricted SARS-specific CD8+ T cells. Using T cell receptor gene transfer, we generated SARS-specific redirected T cells from the lymphocytes of normal individuals. These engineered CD8+ T cells displayed avidity and functionality similar to that of natural SARS-specific memory CD8+ T cells. They were able to degranulate and produce gamma interferon, tumor necrosis factor alpha, and macrophage inflammatory proteins 1α and 1β after antigenic stimulation. Since there is no effective treatment against SARS, these transduced T cells specific for an immunodominant SARS epitope may provide a new avenue for treatment during a SARS outbreak. 相似文献
15.
Human anti-porcine T cell response: blocking with anti-class I antibody leads to hyporesponsiveness and a switch in cytokine production. 总被引:1,自引:0,他引:1
H DerSimonian L Pan C Yatko A Rodrigue-Way E Johnson A S Edge 《Journal of immunology (Baltimore, Md. : 1950)》1999,162(12):6993-7001
Intervention in the molecular interactions that lead to an immune response is possible at various stages of Ag recognition and T cell activation. Perturbation of the interaction of the TCR with the MHC/peptide ligand complex is one approach that has shown promise for autoimmunity and graft rejection in blocking T cell-activated responses. In this study, we investigated the effect of altering the target MHC class I molecule by blocking with Abs. We established a system that analyzed the human T cell response against MHC class I+/class II- porcine stimulatory cell targets. The primary human response against porcine smooth muscle cells was CD8+ T cell dependent. In the presence of F(ab')2 fragments of the MHC class I-reactive Ab, PT-85, the proliferative response was inhibited and production of IL-2 and IFN-gamma was blocked. Moreover, in a secondary response, proliferation was reduced and type 1 cytokine levels were inhibited. In contrast, levels of IL-10 and IL-4 were sustained or slightly increased. These findings indicate that Ab against MHC class I blocked the recognition of porcine cells by the human CD8+ T cells and altered the cytokine secretion profile. Thus, a single treatment with PT-85 F(ab')2 directed against the MHC class I molecule provides an attractive approach to the induction of T cell tolerance that may provide long-term graft survival in porcine-to-human cell transplantation. 相似文献
16.
The response of highly enriched populations of human T8+ lymphocytes to the oxidative mitogenic enzymes neuraminidase (NA) and galactose oxidase (GO) was enhanced by NAGO-primed T4+ lymphocytes. No similar enhancement occurred when the cells were primed with phytohemagglutinin (PHA). In the absence of subclass contamination (1%), the T8+ and T4+ cells responded equally to NAGO by the criterion of DNA replication. The addition of a small number, 2-10%, of NAGO-T4+ cells to the NAGO-T8+ cells enhanced DNA synthesis by as much as 8.5-fold. Augmentation of the cellular response did not occur unless the T4+ cells were activated by NAGO. The converse situation, 2-10% of NAGO-T8+ cells in a primarily NAGO-T4+ cell population, did not increase the DNA synthetic response of the NAGO-T4+ cells. The NAGO-T4+ cells did not augment the early event of increased phosphatidylinositol metabolism or the midcycle event of induction of receptors for interleukin 2 (IL2) and transferrin. The NAGO-T4+ cells therefore increased the probability that fully activated T8+ lymphocytes crossed the G1/S boundary. The basis for this effect was not an enhanced responsiveness of the NAGO-T8+ cells to IL2 or to other soluble growth mediators in medium conditioned by NAGO-activated lymphocytes. The results of this investigation thus implicate a control point in the NAGO-T8+ lymphocyte cell cycle that is positively modulated by the NAGO-T4+ cells themselves or by a product of their activation. 相似文献
17.
Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4. 总被引:72,自引:0,他引:72
L Chen S Ashe W A Brady I Hellstr?m K E Hellstr?m J A Ledbetter P McGowan P S Linsley 《Cell》1992,71(7):1093-1102
Interaction of the B7 molecule on antigen-presenting cells with its receptors CD28 and CTLA-4 on T cells provides costimulatory signals for T cell activation. We have studied the effects of B7 on antitumor immunity to a murine melanoma that expresses a rejection antigen associated with the E7 gene product of human papillomavirus 16. While this E7+ tumor grows progressively in immunocompetent hosts, cotransfection of its cells with B7 led to tumor regression by a B7-dependent immune response mediated by CD8+ cytolytic T lymphocytes. The immune response induced by E7+B7+ tumor cells also caused regression of E7+B7- tumors at distant sites and was curative for established E7+B7- micrometastases. Our findings suggest that increasing T cell costimulation through the CD28 and CTLA-4 receptors may have therapeutic usefulness for generating immunity against tumors expressing viral antigens. 相似文献
18.
Biological activities of the matrix glycoprotein thrombospondin-1 (TSP1) are cell type specific and depend on the relative expression or activation of several TSP1 receptors. Although engaging individual TSP1 receptors in T lymphocytes can elicit costimulating signals, in this study we show that intact TSP1 inhibits TCR-mediated T cell activation, assessed globally using cDNA microarrays. TSP1 signaling suppressed expression of several genes induced in Jurkat T cells, including the T cell activation markers CD69, early growth response gene-1 (Egr-1), and phosphatase of activated cells (PAC-1). TCR-stimulated and CD47-costimulated IL-2 secretion and cell surface CD69 expression were also inhibited by TSP1. The specific inhibitory effect of TSP1 was verified in freshly isolated human PBMCs. TSP1 inhibited TCR-mediated but not protein kinase C-mediated T cell activation. Using CD69 expression as a marker, we demonstrated that the inhibitory activity of TSP1 depended on two TSP1 receptors, CD47 and integrin-associated protein heparan sulfate proteoglycans. Signals from these receptors inhibited TCR signaling downstream of ZAP70, but upstream of NF-AT. Therefore, the expression of TSP1 induced during wound repair and in tumor stroma may limit T cell activation at these sites. 相似文献
19.
J Aramburu M A Balboa A Ramírez A Silva A Acevedo F Sánchez-Madrid M O De Landázuri M López-Botet 《Journal of immunology (Baltimore, Md. : 1950)》1990,144(8):3238-3247
In the present study we describe a novel functional cell surface molecule, designated as Kp43, which is expressed among leukocytes by NK cells, TCR-gamma/delta + T lymphocytes, and some CD8+ CD56+TCR-alpha/beta + T cell clones. The Kp43 Ag is a 70-kDa disulfide-linked dimer, which migrates in SDS-PAGE under reducing conditions as a single 43-kDa band. Two-color immunofluorescence staining of fresh PBL revealed that only a fraction of CD16+, and of TCR-gamma/delta + T lymphocytes expressed the Ag. The analysis of TCR-alpha/beta + T cell clones showed that a small proportion (2 out of 20) weakly expressed Kp43 together with the CD8 and CD56 molecules. By immunoperoxidase staining of different tissues the anti-Kp43, reactivity was detected exclusively in lymphoid organs, where a minority of scattered cells was stained, and in some liver sinusoidal cells. Essentially all NK cells acquired Kp43 when stimulated with a B lymphoblastoid cell line. By contrast, the pattern of distribution of Kp43 remained stable upon in vitro culture of T-gamma/delta lymphocytes, thus delineating two subsets according to its expression. In lymphokine-activated killer populations, obtained by culturing either PBL or NK cells with high concentration of IL-2, most CD16+ and CD56+ cells became Kp43+. The Kp43-specific mAb inhibited the IL-2-dependent proliferative response of cultured NK and TCR-gamma/delta + T cells without affecting their non-MHC-restricted cytotoxicity. The partial inhibitory effect, which was mediated as well by pepsin digested F(ab')2 fragments, was lost upon reduction to Fab. The anti-Kp43 mAb did not interfere with the specific binding of IL-2 to its surface receptors. Altogether the data point out that the Kp43 dimer is involved in the regulation of the IL-2-dependent proliferative response of NK cells and a subset of TCR-gamma/delta + T lymphocytes. 相似文献
20.
Gwinn WM Damsker JM Falahati R Okwumabua I Kelly-Welch A Keegan AD Vanpouille C Lee JJ Dent LA Leitenberg D Bukrinsky MI Constant SL 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(7):4870-4879
Extracellular cyclophilins have been well described as chemotactic factors for various leukocyte subsets. This chemotactic capacity is dependent upon interaction of cyclophilins with the cell surface signaling receptor CD147. Elevated levels of extracellular cyclophilins have been documented in several inflammatory diseases. We propose that extracellular cyclophilins, via interaction with CD147, may contribute to the recruitment of leukocytes from the periphery into tissues during inflammatory responses. In this study, we examined whether extracellular cyclophilin-CD147 interactions might influence leukocyte recruitment in the inflammatory disease allergic asthma. Using a mouse model of asthmatic inflammation, we show that 1) extracellular cyclophilins are elevated in the airways of asthmatic mice; 2) mouse eosinophils and CD4+ T cells express CD147, which is up-regulated on CD4+ T cells upon activation; 3) cyclophilins induce CD147-dependent chemotaxis of activated CD4+ T cells in vitro; 4) in vivo treatment with anti-CD147 mAb significantly reduces (by up to 50%) the accumulation of eosinophils and effector/memory CD4+ T lymphocytes, as well as Ag-specific Th2 cytokine secretion, in lung tissues; and 5) anti-CD147 treatment significantly reduces airway epithelial mucin production and bronchial hyperreactivity to methacholine challenge. These findings provide a novel mechanism whereby asthmatic lung inflammation may be reduced by targeting cyclophilin-CD147 interactions. 相似文献