共查询到20条相似文献,搜索用时 31 毫秒
1.
A Muckerheide P L Domen J G Michael 《Journal of immunology (Baltimore, Md. : 1950)》1987,138(9):2800-2804
Immunoregulatory effects of cationized bovine serum albumin (cBSA) and native bovine serum albumin (nBSA) have been investigated. Intravenous administration of nBSA to BDF1 mice substantially suppressed the antibody response to subsequent immunization with either nBSA or cBSA, whereas pretreatment with cBSA by the same route significantly enhanced the responses to both antigens. The functional properties of BSA-specific T and B cells from mice immunized with cBSA or nBSA were examined in reconstitution experiments in which splenic T populations together with B cells were transferred into irradiated syngeneic recipients. Transfer of splenic T cells from mice primed with nBSA caused profound suppression of the response to subsequent immunization with nBSA or cBSA, whereas transfer of either B or T cells from cBSA treated mice produced an enhanced response to both antigens. C57BL/6 mice, which are considered to be low responders to BSA, produced a significant antibody response to BSA when immunized with cBSA. In contrast, immunization with nBSA did not produce measureable amounts of antibody in mice of this strain. Our data clearly demonstrate that cationized BSA exhibits unique immunogenic properties due to alterations in the self-regulation of the immune response. 相似文献
2.
A Muckerheide R J Apple A J Pesce J G Michael 《Journal of immunology (Baltimore, Md. : 1950)》1987,138(3):833-837
We have shown that a cationized form of bovine serum albumin (BSA) produced by substituting anionic side chain carboxylic groups with aminoethylamide groups possesses unique immunologic properties. The two forms of antigen, native (nBSA) and cationized (cBSA), cross-react at the level of the B cell, as evidenced by the ability of antibody raised against one form to react with the other and by inhibition assays using ELISA. T cell cross-reactivity was also observed in proliferation assays, but the amount of cBSA required for stimulation was 500 times less than the amount of native protein needed. In vivo, cBSA produced responses which, at their optimal levels, were at least double the response to nBSA and which showed a different kinetic pattern, peaking later and lasting longer than the response to the native molecule. Moreover, antibodies were produced in response to administration of cBSA but not nBSA when given i.v. in saline, without an adjuvant. Although a mechanism for these phenomena is not yet clear, we speculate that the cBSA may have a greater affinity for antigen-presenting cells or for the T cell receptor, or that the altered structure may enhance recognition of the molecule by APC and/or helper T cells. 相似文献
3.
Effect of gamma radiation on resting B lymphocytes. II. Functional characterization of the antigen-presentation defect 总被引:4,自引:0,他引:4
J D Ashwell M K Jenkins R H Schwartz 《Journal of immunology (Baltimore, Md. : 1950)》1988,141(8):2536-2544
The effect of radiation on three discrete Ag-presentation functions in resting B cells was examined: 1) Ag uptake and processing, 2) expression of processed Ag in the context of functional class II molecules, and 3) provision of necessary co-stimulatory, or "second," signals. Analysis of radiation's effect on B cell presentation of intact vs fragmented Ag or its effect on presentation by Ag-pulsed B cells indicated that damage to Ag uptake and processing could not account for the bulk of the radiation-induced Ag-presentation defect. Experiments with phosphatidylinositol hydrolysis as an indirect measure of TCR occupancy suggested that irradiation caused a fairly rapid (within 1 to 2 h) decrease in the ability of the B cell APC to display a stimulatory combination of Ag and class II molecule. Ag dose-response analyses demonstrated that when presenting a fragment of the Ag pigeon cytochrome c to a T cell clone, 3000 rad-treated B cell APC were able to stimulate approximately 50% as much phosphatidylinositol turnover as unirradiated B cells. It was also found that, in contrast to their inability to initiate T cell proliferation, and similarly to chemically cross-linked splenocytes, heavily irradiated resting B cells plus Ag induced a state of Ag hyporesponsiveness in T cell clones. This effect on T cells had the same Ag- and MHC-specificity as did receptor occupancy required for proliferation, indicating that heavily irradiated resting B cells bear functional class II molecules. Co-culture of T cells with allogeneic B cells and syngeneic heavily irradiated B cells or chemically cross-linked splenic APC plus Ag resulted in T cell proliferation and interfered with the induction of the hyporesponsive state. This co-stimulatory function was radiosensitive in resting allogeneic B cells. Together, these data support the hypothesis that the major functional consequences of radiation to resting B cell APC are a reduction in the effective display of Ag plus class II molecules and, probably what is more important, a loss in the ability to provide APC-derived co-stimulatory signals. 相似文献
4.
The ability of an adherent Ia+, interleukin 1+ (IL-1) tumor cell line (P388AD) to present turkey gamma-globulin (TGG) to primed T lymphocytes was demonstrated and compared with normal antigen-presenting cells (APC) found in mouse spleen. P388AD tumor cells presented TGG to long-term cultures of TGG-reactive T cells (LTTC) and to lymph node-derived T cells which were enriched on nylon wool columns and subsequently depleted of endogenous antigen-presenting cells with anti-Ia antisera and complement. MHC-restricted antigen presentation by P388AD was observed when long-term cultures of TGG-reactive T cells were used as the responding T-cell population. Furthermore, antisera directed against I-region determinants expressed on the P388AD tumor cells inhibited TGG-specific T-cell proliferation in a dose-related fashion, suggesting a functional role for the tumor cell-associated Ia molecules. The kinetics of antigen presentation to LTTC by P388AD were similar to the kinetics observed for splenic APC, although the magnitude of the proliferative response to LTTC to TGG was generally lower when antigen (Ag) was presented by the tumor cells compared to splenic antigen-presenting cells (APC). However, the magnitude of T-cell proliferation of immune lymph node (LN) T cells was comparable when Ag was presented on tumor cells or splenic APC. Several experiments suggested that Ag uptake and/or processing may be less effective in P388AD tumor cells as compared to normal splenic APC. A nonadherent Ia+, IL-1- tumor cell line (P388NA), which was isolated from the same parental tumor as P388AD, was also tested for the ability to present Ag to primed T lymphocytes and Ag-reactive LTTC. In contrast, to P388AD, the nonadherent tumor cell failed to present TGG under identical culture conditions even though Ia molecules were expressed on the tumor cells and Ag uptake had occurred. However, the defect in Ag presentation by P388NA could be corrected if an exogenous source of purified interleukin 1 was supplied to the cultures. A unique opportunity thus exists with both the P388AD and P388NA tumor cell lines to decipher some of the molecular interactions leading to T-cell proliferation during antigen presentation. 相似文献
5.
Preparations of bovine serum albumin (BSA) were cationized by substituting anionic side chain carboxyl groups with polycationic aminoethylamide groups. Different degrees of substitution were obtained by varying the reaction time. Mice immunized with partially cationized proteins produced early increased levels of antibody over those made by mice immunized with nBSA, followed by a period of decreased response before returning to a second period of enhanced and prolonged antibody synthesis. In contrast, fully substituted BSA gave rise to a significantly enhanced response which was delayed in its onset. Differences in isotype or in antibody specificity during the early and late periods of enhanced responsiveness could not be demonstrated. Cell transfer experiments showed that T cells harvested from mice immunized with the less cationized cBSA preparations could, in contrast to T cells from mice immunized with the fully cationized preparations, suppress antibody responses to both nBSA and cBSA in normal mice. These data are consistent with the possibility that the partially cationized proteins, in contrast to the fully cationized antigen, yield a unique pattern of responsiveness due to retention of determinants necessary for the induction of Ts while exhibiting the enhanced immunogenicity characteristic of cationized molecules. 相似文献
6.
E Roosnek S Demotz G Corradin A Lanzavecchia 《Journal of immunology (Baltimore, Md. : 1950)》1988,140(12):4079-4082
With the use of flow cytometry, we recorded changes in intracellular ionized calcium [Ca2+]i of Indo-1 loaded T cells that were triggered by contact with APC. This rapid readout of TCR perturbation enabled us to monitor the formation of stimulatory Ag-MHC complexes on EBV-transformed B cells that were either pulsed with native tetanus toxoid (TT) or with a 12-amino-acid fragment of this protein. Neither unpulsed APC nor Ag-specific APC that were pulsed with native Ag and kept at +4 degrees C were able to induce changes in basal T cell [Ca2+]i in TT-specific T cell clones. After 1 h at 37 degrees C, however, the Ag-pulsed APC were able to induce a three-to-fourfold increase in [Ca2+]i. This length of time appeared to be almost independent of the concentration of Ag with which the APC were pulsed, suggesting that the lag time was due more to intracellular transit than to association of the processed Ag with the MHC molecule. Furthermore, the same lag time and independence of Ag concentration were found when the EBV-transformed B cells were pulsed with a mouse-anti-transferrin receptor mAb and tested for their capacity to trigger a T cell clone specific for processed mouse Ig. This indicates that, in addition to surface Ig, other receptors that are internalized can function in the same fashion in the uptake and processing of a soluble Ag. In contrast to what was found with intact native Ag, no lag time was observed when the APC were pulsed with high concentrations of a 12-amino-acid peptide, containing the amino acid sequence recognized by a TT-specific T cell clone, suggesting that the formation of MHC-peptide complexes occurs instantly. Pulsing with a lower peptide concentration, however, caused the appearance of a time-dependent increase in efficacy of Ag presentation, suggesting a slow accumulation of MHC-peptide complexes on the B cell membrane. 相似文献
7.
Antigen-presenting cell-T cell interaction in the chicken is MHC class II antigen restricted 总被引:4,自引:0,他引:4
O Vainio T Veromaa E Eerola P Toivanen M J Ratcliffe 《Journal of immunology (Baltimore, Md. : 1950)》1988,140(9):2864-2868
The involvement of the MHC in the recognition of Ag by avian T lymphocytes was analyzed. PBL from chickens primed with keyhole limpet hemocyanin in vivo were induced to synthesize DNA in an in vitro response to specific Ag. Responding cells were T cells as judged by immunofluorescence staining. In vivo Ag-primed PBL were stimulated in vitro with specific Ag and further propagated in the presence of IL-2. Subsequent Ag-specific T cell proliferation required the presence of Ag-pulsed peripheral blood adherent cells (APC). T cell responses were restricted by the MHC of the APC; Ag presented by allogeneic APC did not support T cell proliferation. By using MHC-recombinant chicken lines, the gene products controlled by MHC class II loci were shown to restrict the T cell-APC interaction. This conclusion was substantiated by the inhibition of the Ag-specific T cell response by a mAb against chicken MHC class II gene products but not by a mAb against chicken MHC class I gene products. 相似文献
8.
P L Domen A Muckerheide J G Michael 《Journal of immunology (Baltimore, Md. : 1950)》1987,139(10):3195-3198
The immunoregulatory effects of oral pretreatment of BDF1 mice with cationized bovine serum albumin (cBSA) and native bovine serum albumin (nBSA) have been compared. Oral administration of nBSA suppressed the antibody response to both forms of the antigen. In contrast, oral pretreatment with cBSA greatly enhanced the anti-BSA response in animals subsequently challenged i.p. with either the cationized or native form of the molecule. The enhancement observed with cBSA pretreatment was more pronounced than the suppression observed with the same amount and number of feedings of nBSA. As little as a single oral dose of 10 mg of cBSA produced a significant increase in antibody concentration. Cell transfer of spleen cells into irradiated syngeneic recipients demonstrated that both T cells and B cells were involved in the generation of the response, with a greater degree of enhancement provided by cBSA-pretreated T cells. These data extend our previous findings and demonstrate that administration of cBSA by a normally "tolerogenic" route results in enhancement rather than suppression of the immune response. 相似文献
9.
P E Jensen 《Journal of immunology (Baltimore, Md. : 1950)》1989,143(2):420-425
Th cells recognize a processed form of Ag in association with class II histocompatibility molecules expressed on the surface of APC. The physical nature of the cell surface association of physiologically processed Ag was investigated by using membranes isolated from Ag-pulsed APC. Such membranes were sufficient to directly activate class II-restricted T cell hybridomas without further Ag processing. T cell-stimulating activity remained after treatment of membranes in harsh conditions, including pH 4.0, pH 9.0, high salt, and chaotropic solvents. Activity was lost after exposure to pH 2.0 or protease. The capacity of pH 2.0 (but not protease) treated membranes to present artificially processed, peptide Ag to T cells suggests that exposure to pH 2.0 results in the selective dissociation of processed Ag from membranes. Similar results were obtained in parallel experiments with peptide-pulsed membranes. No qualitative differences were found between physiologically processed Ag and peptide Ag with respect to their remarkably stable association with the APC plasma membrane. 相似文献
10.
Time dependence of B cell processing and presentation of peptide and native protein antigens 总被引:2,自引:0,他引:2
E K Lakey L A Casten W L Niebling E Margoliash S K Pierce 《Journal of immunology (Baltimore, Md. : 1950)》1988,140(10):3309-3314
Th cell recognition of globular proteins requires the uptake and intracellular processing of the native Ag by an APC to produce a peptide fragment containing the T cell antigenic determinant, which is recognized in conjunction with Ia. This report describes the time course of the processing and presentation of a soluble globular protein Ag, pigeon cytochrome c (Pc), and of the presentation of a C-terminal peptide fragment of Pc, residues 81 to 104 (Pc 81-104), which does not require processing. Splenic B cells, acting as APC, require 6 to 8 h incubation with native Pc to process and present it to an I-Ek-restricted Pc-specific T cell hybrid, resulting in the secretion of IL-2. Moreover, the time required for B cells to process Pc is the same whether the Ag is taken up by nonspecific fluid phase pinocytosis or by binding to surface Ig. Once processed, Ag is lost from the B cell surface by 8 to 12 h, although when provided with fresh Pc, the same B cells are still capable of processing and presenting. In contrast to native Pc, only 1 to 2 h are required for the peptide fragment Pc 81-104 to become associated with B cells in a stimulatory fashion, and this time is similar for live and paraformaldehyde-fixed B cells, which cannot internalize or process the peptide. Washed free of excess peptide after 2 h, B cells lose their ability to stimulate T cells by 8 to 12 h, with a time course indistinguishable from that for the loss of processed native Pc. Prolonged incubation of B cells with the peptide for 18 to 24 h results in a dramatic loss of the ability to present Pc 81-104. Even when provided with fresh Pc or Pc 81-104, these cells have diminished ability to present these Ag. This loss is selective, inasmuch as these B cells remain equivalent to untreated B cells in the presentation of an unrelated Ag, OVA, to an I-Ak-restricted specific T cell. However, the ability to present another I-Ek-restricted antigenic peptide of the D glycoprotein of HSV to its specific T cell is also diminished. Loss of activity is observed after incubation only with the peptide and not with the native protein and is not due to a depletion of the antigenic peptide from the incubation medium.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
11.
Constitutive competition by self proteins for antigen presentation can be overcome by receptor-enhanced uptake 总被引:1,自引:0,他引:1
The cells recognize a bimolecular ligand composed of a self Ia molecule and a fragment of foreign Ag that has been processed by an APC. The effect of self proteins on the processing and presentation of foreign Ag was examined in order to ascertain the mechanisms for competition between foreign and self Ag. How this competition can be overcome to allow an efficient immune response was also examined. Normal mouse serum proteins (NMS) compete for the processing and presentation of the foreign Ag bovine RNase by APC. This competition could have occurred at any of three levels in the APC: 1) Ag uptake, 2) Ag processing, or 3) the binding of Ag to an Ia molecule. No competition for either the uptake or the processing of RNase by self proteins could be demonstrated. However, self peptides do compete with foreign Ag by binding directly to Ia molecules, as has been shown previously. Thus, the observed inhibition by NMS of Ag presentation occurred because of competition for binding to the Ia molecule. We hypothesized that during the generation of an immune response this competition is overcome by enhanced uptake of foreign Ag. To test this, we compared the ability of NMS to compete for the presentation of RNase when it entered the APC via fluid-phase pinocytosis or through receptor-mediated uptake via the mannose receptor. When the RNase entered the APC through the mannose receptor, the ability of NMS to compete was dramatically reduced. Thus, self proteins constitutively compete for the presentation of foreign Ag at the level of binding to an Ia molecule, and this competition can be overcome by receptor-mediated uptake of the Ag. 相似文献
12.
Y Kato Y Tanaka F Miyagawa S Yamashita N Minato 《Journal of immunology (Baltimore, Md. : 1950)》2001,167(9):5092-5098
Human Vgamma2/Vdelta2(+) gammadelta T cells respond to low molecular-mass nonpeptide Ags in a gammadelta TCR-dependent manner. Although requirements of Ag presentation have remained controversial, we have indicated that specific responses of the primary gammadelta T cells to pamidronate were dependent on monocytic adherent cells for Ag presentation. Here, we show that human tumor cells can efficiently present aminobisphosphonate and pyrophosphomonoester compounds to gammadelta T cells, inducing specific proliferation and IFN-gamma production. gammadelta TCR dependency of the response to Ag-pulsed tumor cells was confirmed by using a Jurkat line transfected with a Vgamma2/Vdelta2 gammadelta TCR. Furthermore, gammadelta T cells exhibited markedly enhanced cytotoxicity against the Ag-pulsed tumor cells as compared with untreated tumor cells. Survey of a number of human tumor cell lines of different origins revealed that the majority of them became susceptible for gammadelta T cell-mediated cytotoxicity following the Ag pulsing except for breast cancer lines so far examined, while normal PHA blast cells remained resistant. The results not only imply a unique mode of nonpeptide Ag recognition by human gammadelta T cells but also may provide a novel strategic clue for immunotherapy of human malignancy. 相似文献
13.
B S Fox D Dordai R L Moore B E Lacy 《Journal of immunology (Baltimore, Md. : 1950)》1989,143(12):3887-3893
This paper describes an adjuvant-free immunization regimen that results in the priming of T cells but not B cells. B10.A mice were primed s.c. with syngeneic spleen cells that had been pulsed with the peptide 81-104 derived from pigeon cytochrome c. The T cell response was measured by using a sensitive limiting dilution assay that measures lymphokine production. The precursor frequency of Ag-specific cells found in these mice was indistinguishable from the frequency found in mice primed in the footpads with 81-104 in CFA. A striking difference in antibody induction was found, however, when these two immunization regimens were compared. Mice primed with 81-104 in CFA developed significant serum antibody responses against the peptide, whereas mice primed with Ag-pulsed spleen cells produced no detectable anti-peptide antibodies. This lack of antibody did not result from detectable differences in the T cells that were primed: no differences were seen in IL-2 and IL-4 production or in the ability to provide help to B cells in vitro. In vitro stimulation with LPS suggested that the B cells were not primed by the Ag-pulsed spleen cells. The B cells were not tolerized, however, because boosting the mice with Ag in CFA resulted in the induction of an antibody response. The failure to induce an antibody response by priming with Ag-pulsed spleen cells was not caused by the site of immunization or the total amount of Ag used for priming. The critical variable may be the introduction of the Ag on the surface of an APC; in this form, B cell Ag recognition was apparently inefficient, whereas T cell Ag recognition was optimal. 相似文献
14.
CD28 delivers a costimulatory signal involved in antigen-specific IL-2 production by human T cells. 总被引:52,自引:0,他引:52
M K Jenkins P S Taylor S D Norton K B Urdahl 《Journal of immunology (Baltimore, Md. : 1950)》1991,147(8):2461-2466
CD4+ T cells require two signals to produce maximal amounts of IL-2, i.e., TCR occupancy and an unidentified APC-derived costimulus. Here we show that this costimulatory signal can be delivered by the T cell molecule CD28. An agonistic anti-CD28 mAb, but not IL-1 and/or IL-6, stimulated T cell proliferation by tetanus toxoid-specific T cells cultured with Ag-pulsed, costimulation-deficient APC. Furthermore, the ability of B cell tumor lines to provide costimulatory signals to purified T cells correlated well with expression of the CD28 ligand B7/BB-1. Finally, like anti-CD28 mAb, autologous human APC appeared to stimulate a cyclosporine A-resistant pathway of T cell activation. Together, these results suggest that the two signals required for IL-2 production by CD4+ T cells can be transduced by the TCR and CD28. 相似文献
15.
Differential ability of fixed antigen-presenting cells to stimulate nominal antigen-reactive and alloreactive T4 lymphocytes 总被引:3,自引:0,他引:3
The capacity of paraformaldehyde-fixed human antigen-presenting cells (APC) to induce responses by autologous, freshly isolated peripheral blood T4 cells was examined and was compared with their ability to stimulate allogeneic T4 cell DNA synthesis. Fixation of glass-adherent cells (AC) with as little as 0.06% paraformaldehyde abolished leucine incorporation, whereas fixation with 0.75% paraformaldehyde caused death of greater than 98% of the AC. Control APC were able to take up and present the soluble antigens streptokinase-streptodornase (SK-SD), tetanus toxoid, or tuberculin-purified protein derivative to autologous Ia-depleted T4 cells. Fixation with greater than 0.06% paraformaldehyde eliminated such ability. When AC were incubated with antigen overnight and were then fixed, however, they were able to present nominal antigen to autologous T4 cells in a genetically restricted manner that was blocked by monoclonal antibodies directed against monomorphic determinants on class II major histocompatibility complex (MHC) molecules. Despite the ability to present nominal antigen, paraformaldehyde-fixed AC were unable to induce allogeneic T4 cell proliferation. Similar results were observed when non-T cells or spleen cells were used as stimulators. The inability of fixed APC to stimulate allogeneic T4 cell DNA synthesis was not reversed by increasing the number of fixed APC or by the addition of control AC autologous to the responding cells. Moreover, interleukins 1 and 2 either alone or in combination also failed to permit maximal T cell proliferation in response to fixed allogeneic APC. The differential effects of fixation on nominal antigen and alloantigen presentation could not be explained by the loss of membrane thymocyte stimulatory activity on fixed AC. These results indicate that antigen-bearing fixed APC are competent to stimulate proliferation by antigen-reactive T4 cells, but are deficient at inducing allogeneic T4 cell DNA synthesis. The differential sensitivity of these two Ia-restricted functions of APC to chemical denaturation (reductive methylation) by paraformaldehyde suggests that the allodeterminants and restriction elements for nominal antigen on MHC class II molecules can be functionally dissociated. 相似文献
16.
Resting B lymphocytes as APC for naive T lymphocytes: dependence on CD40 ligand/CD40 总被引:4,自引:0,他引:4
Evans DE Munks MW Purkerson JM Parker DC 《Journal of immunology (Baltimore, Md. : 1950)》2000,164(2):688-697
Although resting B cells as APC are tolerogenic for naive T cells in vivo, we show here that they can provide all the costimulatory signals necessary for naive T cell proliferation in vivo and in vitro. In the absence of an activating signal through the B cell Ag receptor, T cell proliferation after Ag recognition on resting B cells depends on CD40 expression on the B cells, implying that naive T cells use the membrane-bound cytokine, CD40 ligand (CD154), to induce the costimulatory signals that they need. Induction of B7-1 (CD80) and increased or sustained expression of CD44H, ICAM-1 (CD54), and B7-2 (CD86) are dependent on the interaction of CD40 ligand with CD40. Transient expression (12 h) of B7-2 is T cell- and peptide Ag-dependent, but CD40-independent. Only sustained (>/=24 h) expression of B7-2 and perhaps increased expression of ICAM-1 could be shown to be functionally important in this system. T cells cultured with CD40-deficient B cells and peptide remain about as responsive as fresh naive cells upon secondary culture with whole splenic APC. Therefore, B cells, and perhaps other APC, may be tolerogenic not because they fail to provide sufficient costimulation for T cell proliferation, but because they are deficient in some later functions necessary for a productive T cell response. 相似文献
17.
Gregerson DS Sam TN McPherson SW 《Journal of immunology (Baltimore, Md. : 1950)》2004,172(11):6587-6597
Although several observations show local T cell recognition of retinal Ag, there has been no direct demonstration that the APC were retinal derived, rather than recruited. In this study, CD45(+) cells isolated from immunologically quiescent murine retina were tested in vitro for functional evidence of Ag presentation to naive and Ag-experienced CD4 T cells specific for beta-galactosidase. Because CD45(+) cells from brain have been reported to be efficient APC, they were included for comparison. Measures of activation included changes in CD4, CD25, CD44, CD45RB, CD62L, CD69, caspase-3 activation, CFSE dilution, size, number of cells recovered, and cytokine production. Retinal CD45(+) cells gave no evidence of Ag-dependent TCR ligation in naive T cells, unlike splenic APC and CD45(+) cells from brain, which supported potent responses. Instead, addition of retinal CD45(+) cells to cocultures of naive 3E9 T cells plus splenic APC reduced the yield of activated T cells and cytokine production by limiting T cell activation at early time points. Ag-experienced T cells responded weakly to Ag presented by retinal CD45(+) cells. Activating the retinal cells with IFN-gamma, anti-CD40, or LPS incrementally increased their APC activity. Addition of neutralizing Abs to TGF-beta did not reveal suppressed retinal APC activity. Because retina lacks tissue equivalents of meninges and choroid plexus, rich sources of dendritic cells in brain, cells from retina may better represent the APC activity of fresh, adult CNS parenchymal and perivascular cells. The activity of the retinal CD45(+) cells appears to be directed to limiting T cell responses. 相似文献
18.
Ocular immune privilege is the result of several unique features of the eye, including the systemic down-regulation of Th1 immune responses to Ags encountered in the anterior chamber of the eye-a phenomenon termed anterior chamber-associated immune deviation (ACAID). The induction of ACAID requires the participation of three cell populations: the ocular ACAID APC, the splenic B cell, and the splenic T cell. Because B cells have been implicated in tolerogenic Ag presentation in other systems, we hypothesized that B cells were responsible for the induction of regulatory T cells in ACAID. The central hypothesis for this study is that APC from the eye migrate to the spleen where they release antigenic peptides (OVA) that are captured and presented to T cells by splenic B cells. A combination of in vitro and in vivo studies demonstrated that splenic B cells, incubated with ACAID APC in vitro, were capable of inducing ACAID when transferred to naive mice. The induction of ACAID required the normal expression of ss(2)-microglobulin on both the B cell and ACAID APC, but not on the T suppressor cells. Moreover, the induction of ACAID regulatory cells required histocompatibility between the B cells and regulatory T cells at the TL/Qa region. The results indicate that: 1) B cells are necessary for the induction of ACAID; 2) ACAID B cells do not directly suppress the expression of delayed-type hypersensitivity; and 3) the induction of Ag-specific regulatory T cells by ACAID B cells requires histocompatibility at the TL/Qa region. 相似文献
19.
Activation requirements of cloned inducer T cells. II. The failure of some clones to respond to antigen presented by activated B cells 总被引:1,自引:0,他引:1
Inducer/helper T cells recognize nominal antigen in association with Ia on the surface of the antigen-presenting cell (APC). Recent studies have shown that B cells can effectively function as APC. In the present study we have assessed the ability of cloned inducer T cells to discriminate between activated B cells or splenic macrophages as APC. We found that most of the clones tested demonstrated an equivalent response to antigen presented by activated B cells or splenic adherent cells. Some clones were very efficiently stimulated by antigen presented by activated B cells, whereas other clones failed to respond or responded very poorly when activated B cells were used to present antigen. We attempted to determine the mechanism responsible for the inability of certain clones to proliferate in response to antigen presented by activated B cells. 相似文献
20.
Production of T-T hybrids from T cell clones. Direct comparison between cloned T cells and T hybridoma cells derived from them 总被引:1,自引:0,他引:1
S Ozaki S K Durum K Muegge J York-Jolley J A Berzofsky 《Journal of immunology (Baltimore, Md. : 1950)》1988,141(1):71-78
It has been assumed, without direct evidence, that T cell hybridomas and non-transformed T cell clones are both good models of normal Ag-specific T cells. To compare directly the difference in activation of cloned normal T cells and T hybridoma cells with the same TCR, cloned T hybridoma cells were obtained by fusing pre-established, myoglobin-specific, Iad-restricted T cell clones (14.5 and 9.27) with BW5147 cells. T cell clones were pre-activated with IL-2 as well as specific Ag before fusion. Cloned T hybridoma A3.4C6 was derived from Lys 140-specific and I-Ed-restricted clone 14.5. The other cloned T hybridoma, C7R14, was a fusion product of Glu 109-specific and I-Ad-restricted clone 9.27. Both T hybridomas showed the same Ag specificity and Ia restriction as the parental cloned T cells. However, C7R14 showed higher apparent affinity and broader cross-reactivity than 9.27. Clone 14.5, but not hybridoma A3.4C6, appeared to stimulate splenic cells to secrete cytokines inhibiting HT-2A cell proliferation. The most striking difference between the clones and hybridomas was that both clones, but neither of the matched hybridomas, were induced to synthesize IL-1 on stimulation with Ag. Finally, both cloned T cells and T hybridomas killed Ag-pulsed Iad-bearing B lymphoma target cells. This evidence suggests that killing function can be inherited from clones to hybridomas. However, the clones were much more efficient at killing than the hybridomas, and the hybridomas were more efficient at IL-2 production than the clones. Thus, matched pairs of clones and hybridomas differ in their capacity to mediate the two functions or may tend to be selected differently during cloning. Thus, although our results generally support the validity of T cell hybridomas as faithful models of the corresponding T cell clones, a number of subtle and not-so-subtle differences indicate that caution must be used in such an extrapolation. 相似文献