共查询到20条相似文献,搜索用时 0 毫秒
1.
Role of antigen-specific B cells in the induction of SRBC-specific T cell proliferation 总被引:12,自引:0,他引:12
In this study, we ask whether antigen presentation can be effected by antigen-activated B cells. Antigen-dependent in vitro proliferation of T cells from mice primed with SRBC or HoRBC occurs in the presence of B cells primed to the relevant antigen. B cells prepared from lymph nodes of mice primed with irrelevant antigens are not effective antigen-presenting cells for RBC-specific T cell proliferation over a wide range of SRBC doses. This is true even when both RBC and the antigen to which the B cells are primed are included in the culture. In contrast, B cells specific for a hapten determinant coupled to SRBC are able to support proliferation of T cells specific for SRBC determinants. We conclude from these data that antigen-specific B cells play a role in the induction of T cell proliferative responses to SRBC and HoRBC antigens. Two models are proposed: either B cells, upon antigen interaction with surface antibody, are able to act as accessory cells to induce Ia-dependent proliferation of immune T cells; or B cells augment the T cell proliferative response by secretion of antibody, leading to opsonization of the antigen for macrophage uptake and presentation. 相似文献
2.
The induction of T cell tolerance in vitro was investigated by using HGG-specific murine helper T cell (Th) clones and cell lines. It was found that exposure of Th to monomeric HGG (tolerogen) for 18 hr rendered the Th unable to reconstitute the PFC response of HGG-primed B cells. The tolerant state was not a result of Th cell death, as up to 100% of Th could be recovered after exposure to the monomer, and in addition, the recovered cells proliferated in response to IL2. B cells were shown not to be significantly affected by the presence of monomeric HGG in amounts calculated to be carried over from the tolerization cultures into the assay cultures. Consequently, it was concluded that interaction between Th and monomeric HGG induced unresponsiveness at the T cell level. A comparison of the tolerogenic potential of monomeric, soluble, and aggregated HGG revealed that only the monomer could induce tolerance in Th. Monomeric HGG was also shown to induce tolerance in an antigen-specific manner. Th reactive to HGG could be tolerized by monomeric HGG, but not Th reactive to FGG or OVA. Helper function of Th was also shown to be antigen specific in that HGG-reactive Th helped only HGG-primed B cells. Certain HGG-specific Th clones were found to be refractory to tolerization with monomeric HGG, whereas other clones derived from the same uncloned cell line were tolerizable. 相似文献
3.
L Ortiz-Ortiz R M Nakamura W O Weigle 《Journal of immunology (Baltimore, Md. : 1950)》1976,117(2):576-579
The question of whether a cell-mediated or a humoral mechanism initiates EAE in rats sensitized with BP-CFA was investigated. The requirement of T cells for EAE induction was manifested when Tx, irradiated rats were reconstituted with normal lymphoid cells treated with ATS and then injected with BP-CFA. Neither EAE nor antibody was produced, indicating the T cell dependency of BP specific antibody production. More precise information regarding the role of the T cell in the production of EAE was obtained by means of passive transfer of EAE with sensitized lymphocytes. Thus, transfer of lymphoid cells from rats previously sensitized to BP-CFA into Tx, irradiated rats elicited EAE and antibodies to BP. However, no EAE followed when the transferred cells were first depleted of T cells by treatment with ATS. Nevertheless, ATP pretreatment did not depress the levels of antibody to BP produced in the transfer recipients. The latter finding indicates that the cells from animals sensitized 9 days previously were already committed to the production of antibodies to BP. Therefore, a) T cells are absolutely necessary for induction of EAE and b) antibody detected by antigen-binding is not responsible for the pathogenesis of this disease. 相似文献
4.
C F Scott M Tsurufuji B Benacerraf M S Sy 《Journal of immunology (Baltimore, Md. : 1950)》1983,131(5):2184-2189
In this paper we have examined the phenomenon of hapten-specific tolerance in the cytolytic T lymphocyte (CTL), using the trinitrophenyl (TNP) and azobenzenearsonate haptens. We found that the H-2 K and H-2 D-end restricted CTL in H-2a mice are differentiable in the ease with which they are tolerized to the TNP hapten. With TNP modified syngeneic spleen cells (TNP-SC), or low amounts of trinitrobenzylsulfonic acid as tolerogen, preferential hyporesponsiveness of D-end restricted CTL can be observed. Larger doses of hapten, e.g. a higher amount of trinitrobenzylsulfonic acid, will tolerize both K- and D-end restricted TNP-specific CTL in H-2a mice. The phenomenon of preferential D-end restricted CTL hyporesponsiveness is not observed in H-2d, H-2k, or H-2b mice, nor is it observed in H-2a mice with respect to the azobenzenearsonate hapten. We have also shown that the clones of CTL responsible for lysis of TNP-modified allogeneic targets (cross-reactive lysis) in H-2a mice probably overlap with the D-end restricted TNP-specific CTL since D-end restricted hyporesponsiveness induced by intravenous injection of TNP spleen cells also results in the elimination of cross-reactive lysis of TNP-modified allogeneic targets. The possible mechanisms of preferential D-end hyporesponsiveness to the TNP hapten in the H-2a mice as well as its significance and relationship to previous work in this area are discussed in this paper. 相似文献
5.
Alteration of T cell subsets and induction of suppressor T cell activity in normal subjects after exposure to sunlight 总被引:3,自引:0,他引:3
P Hersey G Haran E Hasic A Edwards 《Journal of immunology (Baltimore, Md. : 1950)》1983,131(1):171-174
The effects of exposure to natural sunlight on the immune system were studied in 15 normal human subjects. Exposure was for 1 hr each day for 12 days over 2 wk and tests were carried out before, on completion, and 2 wk after completion. In comparison to concurrent studies on 13 age- and sex-matched controls, sun-exposed subjects had a significant increase in their circulation of T cells recognized by OKT8 monoclonal antibodies and a decrease in OKT4 positive T cells. Suppressor T cell activity measured in pokeweed mitogen-stimulated cultures of T and B cells was significantly increased against IgG and IgM production. These changes were still evident in many of the subjects 2 weeks after completion of the sun exposure. A trend for depression of natural killer cell activity against a melanoma target cell was noted in the present study, but this did not appear as marked as that noted previously in subjects exposed to radiation in solariums. The differences between the effect of radiation from solariums and natural sunlight on the immune system may result from the higher dosage of UV-A in radiation from solariums. The results suggest that exposure to sunlight may favor the induction of suppressor pathways in response to antigenic stimuli and that this may limit immune responses against tumor cells such as melanoma. They support the idea from animal studies that systemic changes in the immune system may be an important factor in the association of UV radiation with malignancy. 相似文献
6.
Khalil M Inaba K Steinman R Ravetch J Diamond B 《Journal of immunology (Baltimore, Md. : 1950)》2001,166(3):1667-1674
We have previously reported that immunization with a peptide mimetope of dsDNA on a branched polylysine backbone (DWEYSVWLSN-MAP) induces a systemic lupus erythematosus-like syndrome in the nonautoimmune BALB/c mouse strain. To understand the mechanism underlying this breakdown in self tolerance, we examined the role of T cells in the response. Our results show that the anti-foreign and anti-self response induced by immunization is T cell dependent and is mediated by I-E(d)-restricted CD4(+) T cells of the Th1 subset. In addition, generation of the critical T cell epitope requires processing by APCs and depends on the presence of both DWEYSVWLSN and the MAP backbone. The breakdown in self tolerance does not occur through cross-reactivity between the T cell epitope of DWEYSVWLSN-MAP and epitopes derived from nuclear Ags. In this induced-model of SLE, therefore, autoreactivity results from the activation of T cells specific for foreign Ag and of cross-reactive anti-foreign, anti-self B cells. Despite the fact that tissue injury is mediated by Ab, the critical initiating T cell response is Th1. 相似文献
7.
P Dubois P Stein D Ennist D Greenblatt T Mosmann M Howard 《Journal of immunology (Baltimore, Md. : 1950)》1987,139(6):1927-1934
We report here a role of B cell stimulatory factor 1 (BSF-1) in the induction of antigen-specific proliferation of affinity-purified small B lymphocytes by a thymus-dependent antigen and a carrier-reactive T cell line. By using an ovalbumin-reactive T cell line (designated Hen-1), which does not produce BSF-1 following activation, it was possible to demonstrate that the antigen-specific proliferative response of trinitrophenyl (TNP)-binding B cells to TNP-ovalbumin required exogenous BSF-1 in addition to direct interaction with irradiated Hen-1 T cells. The activation obtained under these conditions was highly efficient, being sensitive to antigen doses as low as 0.001 microgram/ml. The addition of saturating amounts of BSF-1 did not alter the antigen-specificity or the requirements for hapten-carrier linkage or major histocompatibility complex-restricted T-B interaction in this system. The involvement of BSF-1 was confirmed by the ability of 11B11 anti-BSF-1 antibody to specifically suppress the response of TNP-binding B cells to TNP-ovalbumin, BSF-1, and irradiated Hen-1 T cells. Finally, this response was augmented by addition of the monokine interleukin 1. These data indicate that the proliferative response of small B cells to the thymus-dependent antigen and carrier-reactive T cell line used in our experiments can be regulated by the same factors that govern B cell proliferation induced by thymus-independent type 2 antigens or anti-IgM antibodies. 相似文献
8.
Divekar RD Haymaker CL Cascio JA Guloglu BF Ellis JS Tartar DM Hoeman CM Franklin CL Zinselmeyer BH Lynch JN Miller MJ Zaghouani H 《Journal of immunology (Baltimore, Md. : 1950)》2011,187(8):3979-3986
The cell dynamics associated with induction of peripheral T cell tolerance remain largely undefined. In this study, an in vivo model was adapted to two-photon microscopy imaging, and T cell behavior was analyzed on tolerogen-induced modulation. FcγR-deficient (FcγR(-/-)) mice were unable to resist or alleviate experimental allergic encephalomyelitis when treated with Ig-myelin oligodendrocyte glycoprotein (MOG) tolerogen, an Ig carrying the MOG35-55 peptide. However, when FcγR(+/+) dendritic cells (DCs) are adoptively transferred into FcγR(-/-) mice, uptake and presentation of Ig-MOG occurs and the animals were able to overcome experimental allergic encephalomyelitis. We then fluorescently labeled FcγR(+/+) DCs and 2D2 MOG-specific TCR-transgenic T cells, transferred them into FcγR(-/-) mice, administered Ig-MOG, and analyzed both T cell-DC contact events and T cell motility. The results indicate that tolerance takes place in lymphoid organs, and surprisingly, the T cells do not become anergic but instead have a Th2 phenotype. The tolerant Th2 cells displayed reduced motility after tolerogen exposure similar to Th1 cells after immunization. However, the Th2 cells had higher migration speeds and took longer to exhibit changes in motility. Therefore, both Th1 immunity and Th2 tolerance alter T cell migration on Ag recognition, but the kinetics of this effect differ among the subsets. 相似文献
9.
Jae Ho Lee Geunwoong Noh Hyuk Soon Kim Wahn Soo Choi Sangsun Lee 《Cellular immunology》2010,262(1):44-7398
B cells have regulatory functions in immune responses. Antigen-specific responses of B cell subsets by allergen stimulation ex vivo were examined in milk allergy of late eczematous reactions. Eight milk allergy subjects and 13 milk tolerant subjects were selected by DBPCFC. PBMCs were stimulated by casein ex vivo and stained for B cell subsets using monoclonal antibodies. CD19+ B cells unchanged from 8.7 ± 3.8% to 8.0 ± 5.1% (p = 0.504, n = 8) in the milk allergy group and decreased in the milk tolerant group from 8.5 ± 3.2% to 5.0 ± 1.6% (p = 0.001, n = 13). The fraction of apoptotic B cells in B cells significantly decreased 4.4 ± 3.1% to 1.3 ± 0.4% (p = 0.027, n = 4) in the allergy group and insignificantly increased from 2.8 ± 0.6% to 5.4 ± 2.6% (p = 0.059, n = 6) in the milk tolerant group. CD5+ regulatory B1 cell% in B cells decreased in milk allergy subjects from 36.2 ± 5.0% to 31.0 ± 5.7% (p = 0.010) and unchanged in milk tolerant subjects from 41.6 ± 10.2% to 43.8 ± 10.0% (p = 0.413). IL-10 producing CD19+CD5+ regulatory B cell% in CD19+CD5+ regulatory B cells significantly decreased from 24.9 ± 6.5% to 13.8 ± 5.6% (p = 0.002, n = 5) by casein stimulation in milk allergy group and unchanged from 44.8 ± 11.3% to 43.9 ± 10.0% (p = 0.297, n = 5) in the milk tolerant group. B cell subset responses to IL-4 and IL-5 were also similar in both groups. B cell subset changes seemed to have diagnostic value. Exact immunologic roles of regulatory CD5+ B1 cells need further investigation. 相似文献
10.
F Uytdehaag C J Heijnen K H Pot R E Ballieux 《Journal of immunology (Baltimore, Md. : 1950)》1979,123(2):646-653
We intended to investigate whether the suppression of antigen-induced antibody responses in vitro in man by T suppressor cells required contact of T suppressor cells with target cells or whether this effect was mediated by factors released by T suppressor cells. To this end supernatants of antigen-induced T suppressor cells were tested (by a plaque forming cell assay) for their capacity to suppress antibody responses of autologous and allogeneic human peripheral blood lymphocytes. We have shown that supernatants of antigen-specific T suppressor cells, designated as TsF24: a) can suppress an antibody response of autologous but not allogeneic lymphocytes to the inducing antigen; b) are antigen-specific in their effect; and 3) are produced by radiosensitive T cells. Furthermore, the target of the factor is a radiosensitive T cell. These findings taken together indicate that, in the generation of T-effector suppressor cells in man, T-T interactions occur, and in addition, that cellfree factors may be involved in these interactions. 相似文献
11.
Analysis of the requirements for the induction of CD4+ T cell alloantigen hyporesponsiveness by ex vivo anti-CD40 ligand antibody 总被引:8,自引:0,他引:8
Taylor PA Panoskaltsis-Mortari A Noelle RJ Blazar BR 《Journal of immunology (Baltimore, Md. : 1950)》2000,164(2):612-622
A major goal of the transplant field is to selectively tolerize only those donor T cells recognizing host alloantigen and mediating graft-vs-host disease (GVHD). Recently, we described an ex vivo approach in which the blockade of the CD40 ligand (CD40L):CD40 costimulatory pathway in bulk MLR cultures induces donor CD4+ T cells to become specifically tolerant to MHC class II-disparate alloantigenic-bearing stimulators, resulting in a profound reduction in GVHD generation in vivo. In studies presented in this work, we investigated the ex vivo requirements for tolerance induction. We found that CD4+ T cells become profoundly more hyporesponsive to alloantigen restimulation with prolonged culture duration such that 7 to 10 but not 4 days is needed to achieve maximum alloantigen hyporesponsiveness as assessed in secondary MLR cultures and GVHD generation. By day 7, both primed and tolerized cells had substantially increased blastogenesis and CD25 expression. Primed but not tolerized cells substantially down-regulated L-selectin expression, indicating that the tolerized cells do not become fully Ag experienced. Both Th1 and Th2 cytokine production is severely impaired by CD40L:CD40 blockade. Analysis of culture supernatants and results from IL-4 and IL-10 knockout mice indicated that GVHD prevention was not mediated by a skewing toward a Th2 phenotype. The addition of IL-4 to the cultures as a survival factor precluded the induction of tolerance in the anti-CD40L-cultured cells. These data provide further impetus for the ex vivo use of anti-CD40L mAb to block GVHD generation. 相似文献
12.
Antigen-specific and polyclonally induced T cell responses were analyzed in 10 HIV-infected individuals and in 14 controls by enumerating the numbers of tetanus toxoid (TT)-specific and phytohemagglutinin (PHA)-induced IFN-gamma-secreting cells (SC) and IL-4-SC using an enzyme-linked immunospot assay. Whereas the numbers of IFN-gamma-SC in HIV-infected patients were not different from those of the controls in response to an in vitro stimulation with PHA, they were significantly decreased in response to an in vitro stimulation with TT, both before and after a TT booster. Cell depletion experiments indicated that this difference was related to an impairment of CD4(+) T-cell-mediated TT-specific IFN-gamma secretion. Concerning IL-4, the numbers of both polyclonally induced IL-4-SC and TT-specific IL-4-SC were significantly lower in HIV-infected patients than in the controls. It is concluded that secretion of antigen-specific cytokines of both Th1 and Th2 types is depressed in HIV-infected patients. 相似文献
13.
Propagation of antigen-specific T cell helper function in vitro. 总被引:9,自引:0,他引:9
R D Schrier B J Skidmore J T Kurnick S N Goldstine J M Chiller 《Journal of immunology (Baltimore, Md. : 1950)》1979,123(6):2525-2531
Antigen-induced proliferation of primed lymph node cells was abrogated by treatment with anti-Ly 1 serum and complement (C) but not with anti-Ly 2 serum and C. Lymph node cells from animals primed to ovalbumin were activated with antigen in vitro, followed by propagation in an antigen-free supernatant fluid obtained from lectin-induced normal spleen cells. T cells processed in this manner displayed a stepwise enrichment of helper activity for antibody production as measured in a secondary hapten-carrier response. The sequential increase in antigen-specific help was paralleled by a rise in the antigen-induced proliferative response, a phenomenon whose expression was dependent on the presence of syngeneic or semi-syngeneic irradiated filler cells. 相似文献
14.
Involvement of two distinct regulatory T cell populations in the antigen-specific suppression of cytolytic T cell generation. 总被引:2,自引:0,他引:2
B H Devens A W Koontz J A Kapp C W Pierce D R Webb 《Journal of immunology (Baltimore, Md. : 1950)》1991,146(5):1394-1401
Alloantigen-specific, radiation-resistant T cells generated in mixed-lymphocyte cultures inhibited the generation of allospecific CTL responses in vitro. This regulatory T cell population was studied using mAb generated to Ag-specific suppressor factors that regulate the response to the synthetic terpolymer L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT). Both monoclonal 984 D4.6.5 and a pool of four mAb 2441, when added in the presence of complement, eliminated alloantigen-specific inhibition of the CTL response. When separate cell cultures treated with mAb 984 or 2441 plus complement were recombined, inhibition was reestablished, suggesting that two or more populations of cells are required for active inhibition. Furthermore, neither the mAb 984 nor the mAb 2441 plus complement had any effect on any stage of CTL development. This suggests that the inhibition of the CTL response was not the result of cytolytic activity via the regulatory T cells. Experiments in which these antibodies were added without complement treatment showed that the mAb 2441 neutralized the inhibitory activity, whereas mAb 984 augmented inhibition. It is concluded from these studies that regulatory T cells originally identified in humoral immune responses also regulate cell-mediated immune responses. Suppressor epitopes are displayed on the surface of these cells that allow them to be distinguished from other T cells. These data also show the utility of the mAb 984 and 2441 raised against specific suppressor T cell products in different experimental models of immunity. These studies suggest that phenotypically distinct Ts cell populations can play a normal regulatory role in both cell-mediated and humoral immunity. 相似文献
15.
M Shoji M Tachibana K Katayama K Tomita S Tsuzuki F Sakurai K Kawabata KJ Ishii S Akira H Mizuguchi 《Biochemical and biophysical research communications》2012,424(1):89-93
Microtubules in living cells are very important component for various cellular functions as well as to maintain the cell shape. Mechanical properties of microtubules play a vital role in their functions and structure. To understand the mechanical properties of microtubules in living cells, we developed an orthotropic-Pasternak model and investigated the vibrational behavior when microtubules are embedded in surrounding elastic medium. We considered microtubules as orthotropic elastic shell and its surrounding elastic matrix as Pasternak foundation. We found that due to mechanical coupling of microtubules with elastic medium, the flexural vibration is increased with the stiffening of elastic medium. We noticed that foundation modulus (H) and shear modulus (G) have more effect on radial vibrational mode as compared to longitudinal vibrational mode and torsional vibrational mode. 相似文献
16.
CD4+ T cells from lupus-prone mice avoid antigen-specific tolerance induction in vivo 总被引:2,自引:0,他引:2
Activated T cells in spontaneous lupus presumably bypass normal tolerance mechanisms in the periphery, since thymic tolerance appears intact. To determine whether such T cells indeed avoid in vivo peripheral tolerance mechanisms, we assessed their activation and recall responses after in vivo Ag stimulation in the absence of exogenously supplied costimulatory signals. Naive CD4(+) AND (transgenic mice bearing rearranged TCR specific for pigeon cytochrome c, peptides 88-104) TCR-transgenic T cells, specific for pigeon cytochrome c, from lupus-prone Fas-intact MRL/Mp+(Fas-lpr) and from H-2(k)-matched control CBA/CaJ and B10.BR mice (MRL.AND, CBA.AND, and B10.AND, respectively) were adoptively transferred into (MRL x CBA)F(1) or (MRL x B10)F(1) recipients transgenically expressing membrane-bound pigeon cytochrome c as a self-Ag. MRL.AND and control CBA.AND and B10.AND-transgenic T cells were activated and divided after transfer, indicating encounter with their cognate Ag; however, T cells from CBA.AND and B10.AND mice were impaired in their ability to proliferate and produce IL-2 after challenge with pigeon cytochrome c in ex vivo recall assays, a typical phenotype of anergized cells. By contrast, MRL.AND T cells proliferated more, and a significantly higher percentage of such cells produced IL-2, compared with control T cells. This observation that MRL T cells avoided anergy induction in vivo was confirmed in an in vitro system where the cells were stimulated with an anti-CD3 in the absence of a costimulatory signal. These experiments provide direct evidence that CD4(+) T cells from Fas-intact lupus-prone MRL mice are more resistant than nonautoimmune control cells to anergy induction. Anergy avoidance in the periphery might contribute to the characteristic finding in lupus of inappropriate T cell activation in response to ubiquitous self-Ags. 相似文献
17.
The hallmark of adaptive immunity is its ability to recognise a wide range of antigens and technologies that capture this
diversity are therefore of substantial interest. New methods have recently been developed that allow the parallel analysis
of T cell reactivity against vast numbers of different epitopes in limited biological material. These technologies are based
on the joint binding of differentially labelled MHC multimers on the T cell surface, thereby providing each antigen-specific
T cell population with a unique multicolour code. This strategy of ‘combinatorial encoding’ enables detection of many (at
least 25) different T cell populations per sample and should be of broad value for both T cell epitope identification and
immunomonitoring. 相似文献
18.
The aim of this study was to quantitatively compare expression of mRNA for IL-5 and IFN-gamma with the frequency of mRNA-positive cells, total and activated eosinophils, neutrophils, lymphocytes, and vessels expressing adhesion molecules. Replicate biopsies of skin LPR to pollen antigens (Ag) and control injection sites (B) at 6 and 24 h were assessed for: (1) mRNA for IL-5 and IFN-gamma by quantitative RT-PCR (QC-RT/PCR); (2) frequency of cells expressing mRNA for IL-5 and IFN-gamma by in situ hybridization (ISH); (3) inflammatory cells and adhesion molecule expression. More mRNA for IL-5 was found in Ag- than in B-injected sites at 6 and 24 h by both QC-RT/PCR and ISH. Small amounts of mRNA for IFN-gamma were detected in Ag sites by QC-RT/PCR at 6 and 24 h, but were not significantly different than at B sites. The frequency of IFN-gamma mRNA(+)cells was higher in Ag than in B sites at 6 h. There was no correlation between the amount if IL-5 detected by QC-RT/PCR and frequency of IL-5 mRNA(+)cells by ISH. These findings also did not correlate with the degree of inflammatory responses. In conclusion: (1) greater IL-5 than IFN-gamma deposition in Ag sites suggests Th(2)predominance in LPR; (2) lack of correlation between QC-RT/PCR and ISH findings may reflect varying mRNA content of inflammatory cells. 相似文献
19.
T cell expansion typically is due to cognate interactions with specific Ag, although T cells can be experimentally activated through bystander mechanisms not involving specific Ag. TGF-beta1 knockout mice exhibit a striking expansion of CD4+ T cells in the liver by 11 days of age, accompanied by CD4+T cell-dependent necroinflammatory liver disease. To examine whether hepatic CD4+T cell expansion in TGF-beta1(-/-) mice is due to cognate TCR-peptide interactions, we used spectratype analysis to examine the diversity in TCR Vbeta repertoires in peripheral CD4+T cells. We reasoned that Ag-nonspecific T cell responses would yield spectratype profiles similar to those derived from control polyclonal T cell populations, whereas Ag-specific T cell responses would yield perturbed spectratype profiles. Spleen and liver CD4+T cells from 11-day-old TGF-beta1(-/-) mice characteristically exhibited highly perturbed nonpolyclonal distributions of TCR Vbeta CDR3 lengths, indicative of Ag-driven T cell responses. We quantitatively assessed spectratype perturbation to derive a spectratype complexity score. Spectratype complexity scores were considerably higher for TGF-beta1(-/-) CD4+ T cells than for TGF-beta1(+/-) CD4+T cells. TCR repertoire perturbations were apparent as early as postnatal day 3 and preceded both hepatic T cell expansion and liver damage. By contrast, TGF-beta1(-/-) CD4+ single-positive thymocytes from 11-day-old mice exhibited normal unbiased spectratype profiles. These results indicate that CD4+ T cells in TGF-beta1(-/-) mice are activated by and respond to self-Ags present in the periphery, and define a key role for TGF-beta1 in the peripheral regulation of Ag-specific CD4+ T cell responses. 相似文献
20.
Russ AJ Xu K Wentworth L Alam S Meyers JV Macklin MD Rakhmilevich AL Rajamanickam V Suresh M Cho CS 《Cellular immunology》2011,271(1):104-109
We have observed that in vivo interaction between melanoma and resting T cells promotes suppression of antigen-driven proliferative T cell expansion. We hypothesized that this suppression would affect tumor antigen-specific T cell populations more potently than tumor-unrelated T cell populations. A B16F10 cell line was stably transfected to express low levels of the lymphocytic choriomeningitis virus (LCMV) glycoprotein GP33 (B16GP33). Mice bearing B16F10 or B16GP33 tumors were infected with LCMV, and proliferative expansion of LCMV epitope-specific T cell populations was quantified. In vitro and in vivo assays confirmed low levels of antigenic GP33 expression by B16GP33 tumors. Suppressed expansion of GP33-specific T cells was equivalent between mice bearing B16F10 and B16GP33 tumors. These observations suggest that the ability of growing melanoma tumors to impair antigen-driven proliferative expansion of activated T cells is global and not antigen-specific, and provide further insight into the influence of cancer on activated T cell homeostasis. 相似文献