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1.
Ronald Palacios 《Immunogenetics》1981,14(3-4):309-322
The role of HLA-DR antigens in the activation of T cells in the allogeneic mixed lymphocyte reaction (MLR) was studied by using antibodies raised against the alpha, beta or the complex of both chains of the HLA-DR antigens. Antisera directed against the alpha or the beta chain strongly inhibited the T-cell proliferative response when added at the begining of MLR cultures but not 72 h later. T cells from MLR cultures treated with either alpha-chainor beta-chain-specific antibodies did not respond to interleukin-2 (IL-2) by proliferating, whereas T cells from non-anti-DR-treated cultures showed a proliferative response to IL-2 stimulation. However, neither the anti-alpha chain nor the anti-beta chain serum was able to inhibit continuous proliferation of already activated, IL-2-reactive T cells supported by IL-2. In MLR, OKT4+ but not OKT8+ lymphocytes synthesized IL-2. This function was abrogated by the alpha-chain-specific antibody but not by the anti-beta chain serum. Interleukin-1 (IL-1) did not reverse the inhibitory activity on IL-2 synthesis of the alpha-chain antibody, while IL-1 promoted the production of IL-2 in MLR cultures not exposed to the anti-DR sera. In addition, nonstimulated OKT4+ cells were unresponsive to IL-1 and did not produce IL-2. From these results, it is concluded that HLA-DR antigens participate actively in the activation of T cells by allogeneic non-T cells. Thus, both the alpha and beta chains of HLA-DR antigens render resting T cells sensitive to IL-2. In addition, the alpha but not the beta chain participates in the production of IL-2 by enabling OKT4+ lymphocytes to respond to IL-1 and subsequently to synthesize IL-2. Once T cells have acquired responsiveness to IL-2 and this growth factor has been produced there is no further requirement for HLA-DR antigens. Continuous proliferation and growth of IL-2-reactive T cells depends on the availability of interleukin-2. 相似文献
2.
Background and “spontaneous” proliferation are terms often used for the proliferative activity normally exhibited by peripheral blood mononuclear cells (MNC) in vitro. In this report, we show that Interleukin-2 (IL-2) added to unfractionated MNC but not to isolated T or non-T cells significantly increased their proliferative activity. The cells responding to IL-2 stimulation from MNC were OKT3 positive lymphocytes. In addition, treatment of MNC with either a monoclonal anti-HLA-DR antibody (in the absence of C′) or Cyclosporin-A strongly suppressed the “background” whereas treatment of MNC with the 3A1 monoclonal anti-human T cell antibody did not modify “spontaneous” proliferation of these cells. IL-2 could not restore or increase the proliferative activity of MNC exposed to the anti-HLA-DR antibody or Cyclosporin-A while the T cell growth factor significantly enhanced proliferation of MNC cultured in the presence of the OKT4 antibody. Taken together these results strongly suggest that IL-2 responding T cells from MNC become sensitive to IL-2 by interacting with HLA-DR antigens on B lymphocytes and/or monocytes contained in MNC (resting T cells are Dr?). By a similar mechanism we have previously shown that T cells acquire responsiveness to IL-2 in the autologous mixed lymphocyte reaction (AMLR). Since all the cells that participate in AMLR are present in MNC, we postulate that a “mini” AMLR taking place within MNC may explain the “spontaneous” proliferation of peripheral blood mononuclear cells. 相似文献
3.
J P Siegel 《Cellular immunology》1988,111(2):461-472
The role of interferon (IFN)-gamma in the activation of human T cells was investigated. Addition of IFN-gamma to mixed-lymphocyte cultures (MLC) augmented both the proliferation and the development of T-cell-mediated cytotoxicity. IFN-gamma also augmented the early expression on CD8+ but not CD4+ lymphocytes of IL-2 receptor alpha chain (Tac antigen) and Class II major histocompatibility antigen (HLA-DR). This effect synergized with that caused by interleukin 2 and was not observed with IFN-alpha. The addition of neutralizing antibody against IFN-gamma to MLC suppressed the development of cytotoxicity and proliferation and the expression of activation antigens on CD8+ cells. In experiments in which highly purified CD8+ T cells were activated with cell-free stimuli, IFN-gamma slightly but significantly augmented proliferation, antibody to IFN-gamma suppressed proliferation, and excess IFN-gamma reversed this suppression. It is concluded that (i) IFN-gamma augmented activation of T cells in human MLC, (ii) IFN-gamma exerted effects directly on T cells, and (iii) IFN-gamma preferentially augmented CD8+ cell activation. 相似文献
4.
HLA-DR antigens render resting T cells sensitive to interleukin-2 and induce production of the growth factor in the autologous mixed lymphocyte reaction 总被引:12,自引:0,他引:12
Monoclonal anti-HLA-DR (anti-Ia) antibodies inhibited autologous mixed lymphocyte reactions (AMLR) when added from the initiation of the cultures, but not 72 hr later. The suppressive principle was removed by the stimulator non-T cells, but not by the responding T cells. Antibody-treated non-T cells lost their ability to activate T cells, whereas antibody-treated T cells could still respond to untreated non-T cells. The anti-DR antibodies prevented T cells from acquiring responsiveness to Interleukin-2 (IL-2). However, T cells previously activated by AMLR responded to IL-2 even in the presence of the anti-DR antibodies. OKT4+ lymphocytes synthesized IL-2 in the AMLR while OKT8+ cells did not. Anti-DR antibodies caused OKT4+ cells to become unresponsive to Interleukin-1 stimulation and inhibited the production of IL-2. Interleukin-1 (IL-1) promoted the synthesis of IL-2 in non-anti-DR-treated AMLR cultures. Since resting T cells are unresponsive to IL-2 and resting OKT4+ lymphocytes are unable to produce IL-2 even in the presence of IL-1, it is concluded that HLA-DR antigens render resting T cells sensitive to IL-2 and enable OKT4+ lymphocytes to respond to IL-1 and subsequently, to produce Interleukin-2. 相似文献
5.
Cord blood T cells did not produce interleukin 2 (IL-2) nor acquire responsiveness to it in autologous mixed-lymphocyte reaction (AMLR) as they do when activated by phytohemagglutinin (PHA). The ability of the cells to respond to IL-2 was restored either by the addition of recombinant IL-2 to the AMLR culture or by the preculture of non-T stimulator cells with recombinant interferon-gamma (IFN-gamma). IL-2 production was also induced when the T cells were added with recombinant IL-2 at the initiation of the AMLR culture, preceded by the treatment of non-T cells with recombinant IFN-gamma. IL-2-producing cells of cord blood induced in the above-mentioned condition were defined to be OKT4+ T cells, because the deletion of OKT4+ T cells from T-cell population abrogated the reaction, while that of OKT8+ T cells did not. Acquisition of IL-2 responsiveness and IL-2 production of T cells seemed to be mediated by HLA-DR and HLA-DQ molecules of non-T cells because these reactions were blocked by the treatment of non-T cells either with monoclonal anti-HLA-DR or with anti-HLA-DQ antibody. The HLA-DR and HLA-DQ densities of cord blood non-T cells were low as compared with those of adult, but the expression of HLA-DQ was remarkably improved by IFN-gamma treatment. In regard to IL-2, both IFN-gamma and IL-2 were needed to enable the lymphocytes to produce. This may suggest that some functional maturation by IL-2 of responder T cells is further required. These combined data suggested that cord blood non-T cells are defective as a stimulator in AMLR and this could be corrected by enhancing the expression of HLA-DQ antigen. 相似文献
6.
To investigate the specific nature of the autologous mixed lymphocyte reaction (AMLR), we applied a method in which mixtures of NY-nonadherent responder cells and NY-adherent stimulator cells were treated with neuraminidase before culture and then cultured to assay the AMLR. This method produced a marked enhancement of DNA replication in the responder cells and the results were reproducible, regardless of the individuals tested. Using this method, we were able to make the following observations regarding the specific nature of the AMLR. (i) The AMLR is an IL-2-independent reaction, as revealed by bioassay to detect the presence of IL-2 by a blocking test using anti-IL-2R sera and as shown by the absence of mRNA for IL-2 in Northern hybridization. (ii) It is also HLA-DR dependent as proven by the fact that anti-DR sera almost completely inhibited the reaction. (iii) The AMLR was also found to induce the generation of activated CD4+ helper T cells in direct response to stimulation by NY-adherent cells, in which HLA-DR antigens were involved. (iv) Also, it induced the generation of CD4-CD8- double-negative (DN) lymphocytes, including gamma delta T cells with a cytotoxic activity against NK-resistant target cells and with a variety of lymphocyte activation markers (CD56, HLA-DR, CD25, transferrin receptors, CD38, and LFA-1). However, the AMLR did not induce the generation of NK cell markers CD16 and CD57. (v) The DN lymphocytes and gamma delta T cells appeared to be generated from the precursors of CD4-CD8- DN cells, in direct response to the stimulator cells. These results strongly suggest that the AMLR may be a phenomenon which induces the proliferative response of gamma delta T cells and their precursors, in addition to that of alpha beta T cells, particularly of CD4+ helper T cells. 相似文献
7.
Antisera directed against the heavy, the light, or reactive against the complex of both chains of HLA-DR antigens strongly inhibited proliferation of T cells induced by TNP- or FITC-labeled autologous cells when added at initiation of the cultures, but not 72 h later. T cells from cultures treated with the anti-DR sera were unresponsive to interleukin-2 (IL-2). Nonetheless, the anti-DR sera did not inhibit proliferation of T cells that had already acquired sensitivity to IL-2. The DR antibodies abrogated the synthesis of IL-2 induced by both TNP- and FITC-conjugated autologous cells. Treatment of TNP- and FITC-labeled autologous cell cultures with the four different types of anti-DR sera significantly inhibited the induction of cytotoxic T cells. However, DR antibodies added at the effector phase of cytotoxicity assays did not inhibit the cytotoxic activity. Effector T cells from cultures treated with the anti-DR sera were unresponsive to IL-2 and addition of IL-2 to these cultures did not restore the cytotoxic activity. In contrast, effector T cells from cultures performed in the absence of the anti-DR sera proliferated to IL-2 stimulation and addition of IL-2 to these cultures significantly increased the generation of killer cells specific for hapten-labeled self structures. From these results we concluded the following: (1) Both the heavy and the light chains of DR antigens participate actively in the activation of T cells by rendering resting T cells sensitive to IL-2 and by inducing production of the growth factor in TNP- and FITC-conjugated autologous cell cultures. (2) The heavy and light chains of the DR antigens play an essential role in the induction of cytotoxic T cells specific for hapten-labeled self structures, most likely by enabling cytotoxic T cells to respond to IL-2 and by inducing the IL-2 producer T cells to synthesize the growth factor. 相似文献
8.
Interleukin 2 induces proliferation of normal "resting" human T cells in the absence of other known external stimulation 总被引:2,自引:0,他引:2
Interleukin 2(IL-2) is known to stimulate the progression of activated T cells from G1 through the rest of the cell cycle. We have demonstrated that addition of purified recombinant human IL-2 (rIL-2) to fresh normal human peripheral blood mononuclear cells (PBM), which were IL-2 receptor (Tac) negative by FACS analysis, stimulated marked proliferation of the PBM. IL-2-induced proliferation was also observed with umbilical cord blood mononuclear cells. Monocyte depletion of PBM resulted in a marked reduction of rIL-2-induced proliferative response which could be restored by adding back autologous irradiated monocytes but not by interleukin 1. The T cells preincubated with rIL-2 showed a five to six times enhanced autologous mixed-lymphocyte reaction (AMLR) compared to controls. The rIL-2-induced proliferative response of PBM was inhibited in a concentration-dependent fashion by preincubation of PBM with an anti-HLA-DR framework monoclonal antibody. The proliferating cells were shown by two-color flow cytometric analysis to be primarily Leu-1+ and Leu-4+ T cells (both leu-3+ and Leu-2+ subsets); however, 6 to 19% of responding cells had surface markers for B cells or NK cells. The data demonstrate that rIL-2 can induce proliferation of "resting" human T cells. The phenomenon may be related to a monocyte-dependent AMLR which induces IL-2 receptors and IL-2 responsiveness in a subset of T cells. 相似文献
9.
10.
M Kamio N Arima M Tsudo K Imada M Ohkuma T Uchiyama 《Biochemical and biophysical research communications》1992,184(3):1288-1292
It is known that the affinity cross-linking study of the human high-affinity Interleukin 2 (IL-2) receptor reveals triplet bands consisting of 70 kDa alpha chain(Tac)-IL-2 and the 90/80 kDa doublet. We found the cell lines lacking the lower band of the doublet in spite of the expression of both alpha and beta chains. No IL-2 binding was detectable in the presence of anti-Tac antibody in these cells. Immunoprecipitation from the cell extract of [125 I] IL-2-cross-linked T cells with anti-beta chain polyclonal IgG detected the upper band, but not lower band of the doublet. These data suggest that the lower band of the doublet represents an unknown IL-2-binding protein (p65) distinct from the beta chain and this molecule may be involved in the intermediate-affinity IL-2 binding together with the beta chain. 相似文献
11.
Kim SH Reznikov LL Stuyt RJ Selzman CH Fantuzzi G Hoshino T Young HA Dinarello CA 《Journal of immunology (Baltimore, Md. : 1950)》2001,166(1):148-154
IL-18 and IL-12 are major IFN-gamma-inducing cytokines but the unique synergism of IL-18 and IL-12 remains unclear. In the human NK cell line NKO, IL-18R alpha, and IL-18R beta are expressed constitutively but IL-18 did not induce IFN-gamma unless IL-12 was present. COS-1 fibroblasts, which produce the chemokine IL-8 when stimulated by IL-1 beta or TNF-alpha, do not respond to IL-18, despite abundant expression of the IL-18R alpha chain. COS-1 cells lack expression of the IL-18R beta chain. The IL-18R beta cDNA was cloned from a human T-B lymphoblast cDNA library and COS-1 cells were transiently transfected with the IL-18R beta chain and a luciferase reporter. In transfected COS-1 cells, IL-18 induced IL-8 and luciferase in the absence of IL-12 and independently of IL-1 and TNF. Ab against the IL-18R alpha chain, however, prevented IL-18 responsiveness in COS-1 cells transfected with the IL-18R beta chain, suggesting that both chains be functional. In NKO cells and PBMC, IL-12 increased steady-state mRNA levels of IL-18R alpha and IL-18R beta; the production of IFN-gamma corresponded to IL-12-induced IL-18R alpha and IL-18R beta chains. We conclude that functional reconstitution of the IL-18R beta chain is essential for IL-12-independent proinflammatory activity of IL-18-induced IL-8 in fibroblasts. The synergism of IL-18 plus IL-12 for IFN-gamma production is, in part, due to IL-12 up-regulation of both IL-18R alpha and IL-18R beta chains, although postreceptor events likely contribute to IFN-gamma production. 相似文献
12.
The interactions of T-cell receptor with self-Ia antigen on non-T cells induced IL-2 production and IL-2 receptors on the cell surface and thus responsiveness to IL-2 of T cells in autologous mixed-lymphocyte reaction (AMLR). Four-day-cultured autologous non-T cells lost their ability to stimulate T cells to produce and respond to IL-2 with concurrent decrease of HLA-DR and HLA-DQ antigen expressed on the cell surface. Culturing of non-T cells with 500 U/ml of recombinant interferon gamma (IFN-gamma) maintained their stimulating ability which was otherwise lost. Treatment of non-T cells with monoclonal anti-HLA-DR or anti-HLA-DQ antibody before mixture with T cells abrogated their ability to induce IL-2 production and IL-2 responsiveness of T cells. The combined data suggested that Ia antigen expressed on non-T cells is modulated by IFN-gamma, which increases the ability of non-T cells to stimulate autologous T cells to produce and respond to IL-2. 相似文献
13.
Translation and assembly of HLA-DR antigens in Xenopus oocytes injected with mRNA from a human B-cell line. 总被引:7,自引:0,他引:7
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HLA-DR antigens are polymorphic cell surface glycoproteins, expressed primarily in B lymphocytes and macrophages, which are thought to play an important role in the immune response. Two polypeptide chains, alpha and beta, are associated at the cell surface, and a third chain associates with alpha and beta intracellularly. RNA isolated from the human B-cell line Raji was injected in Xenopus laevis oocytes. Immunoprecipitates of translation products with several monoclonal antibodies revealed the presence of HLA-DR antigens similar to those synthesized in Raji cells. One monoclonal antibody was able to bind the beta chain after dissociation of the three polypeptide chains with detergent. The presence of all three chains was confirmed by two-dimensional gel electrophoresis. The glycosylation pattern of the three chains was identical to that observed in vivo, as evidenced in studies using tunicamycin, an inhibitor of N-linked glycosylation. The presence of alpha chains assembled with beta chains in equimolar ratio was further demonstrated by amino-terminal sequencing. An RNA fraction enriched for the three mRNAs, encoding alpha, beta, and intracellular chains, was isolated. This translation-assembly system and the availability of monoclonal antibodies make it possible to assay for mRNA encoding specific molecules among the multiple human Ia-like antigens. 相似文献
14.
Activated human T cells can present alloantigens but cannot present soluble antigens 总被引:3,自引:0,他引:3
Human T cells, when activated by antigen or mitogen, express Ia antigens. We have examined the capacity of activated T cells to stimulate autologous and allogeneic T cells and their ability to present soluble antigen. Interleukin 2-dependent T-cell lines (TCL), free of accessory cells, were used for antigen-presenting cells. These activated T cells were potent stimulators in an autologous mixed lymphocyte reaction (AMLR), more so than autologous irradiated non-T mononuclear cells. Activated T cells were also able to stimulate proliferation of allogeneic T cells in the absence of any other accessory cells, and this stimulation was blocked by anti-Ia antibodies. Resting unstimulated T cells were unable to stimulate autologous or allogeneic responses. Thus, activated T cells were able to present self antigens and alloantigens. However, activated T cells could not present soluble antigens to autologous T cells or to antigen-specific TCL even if exogenous interleukin 1 was added to cultures. The ability of activated T cells to stimulate an AMLR in vitro may reflect an important immunologic amplification mechanism in vivo. The ability of activated T cells to present alloantigens but not soluble antigens suggests an inability to process antigen, and this may provide further insights into the complexities of antigen presentation. 相似文献
15.
Increased human immunodeficiency virus (HIV) expression in chronically infected U937 cells upon in vitro differentiation by hydroxyvitamin D3: roles of interferon and tumor necrosis factor in regulation of HIV production.
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C Locardi C Petrini G Boccoli U Testa C Dieffenbach S Butt F Belardelli 《Journal of virology》1990,64(12):5874-5882
We have investigated the roles of cytokines in the modulation of human immunodeficiency virus (HIV) production in chronically infected U937 cells upon in vitro differentiation by hydroxyvitamin D3. HIV-infected U937 cells exhibited markedly lower levels of CD4 and HLA-DR antigens than uninfected cells did. Vitamin D3 induced a time-dependent macrophagelike differentiation, as determined by monitoring the expression of some surface antigens by means of the monoclonal antibodies OKM1, OKM5, OKM13, OKM14, OKT4, anti-HLA-DR, TecMG2, TecMG3, LeuM3, LeuM1, anti-HLA-DP, and anti-HLA-DQ. Treatment with hydroxyvitamin D3 resulted in a marked increase in HIV production compared with control cultures. Interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha) were detected in the culture media, whereas interferon (IFN) was not generally found. Using the polymerase chain reaction technique, we found HIV-infected U937 cells to express detectable levels of mRNAs for alpha interferon (IFN-alpha), IFN-beta, TNF-alpha, and IL-1 beta. The addition of TNF resulted in a marked increase of HIV production, whereas IL-1 beta was ineffective. In contrast, both IFN-alpha and IFN-beta exerted some inhibitory effect on HIV production, which was more marked in vitamin D3-treated cultures than in untreated cultures. HIV production was significantly increased by antibodies to IFN-alpha in both untreated and vitamin D3-treated cultures. Anti-IFN-beta antibody increased HIV production only in vitamin D3-treated cells. In contrast, anti-TNF-alpha antibodies markedly decreased HIV production in both control and differentiating U937 cells. Vitamin D3 treatment resulted in a higher expression of TNF receptors in differentiating cells than in control HIV-infected cells. These data demonstrate a strong correlation between HIV production and macrophagelike differentiation in chronically infected U937 cells and suggest that endogenous IFN and TNF exert opposite effects in the regulation of virus production in both undifferentiated and vitamin D3-treated cell cultures. 相似文献
16.
Human interferons-alpha, -beta and -gamma enhance HLA-DR mRNAs in all the human lymphoblastoid and melanoma cell lines studied. The increase concerns both alpha and beta chain mRNAs. Moreover, we show that immune interferon-gamma preferentially enhances class II MHC mRNA. This effect of IFN-gamma on the synthesis of alpha and beta HLA-DR chains has been also analysed by immunoprecipitation. It is abolished by a monoclonal antibody directed against human IFN-gamma. The effect of interferon on the cell surface level of HLA-DR molecules does not always correspond to the enhancement of HLA-DR mRNA. Our experiments suggest that this discrepancy between the enhancement of HLA-DR mRNA and cell surface antigen might be due to a constitutively high level of the corresponding antigens on several of the human cells studied. 相似文献
17.
A membrane-proximal region of the interleukin-2 receptor gamma c chain sufficient for Jak kinase activation and induction of proliferation in T cells. 总被引:1,自引:0,他引:1
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The interleukin-2 (IL-2) receptor (IL-2R) consists of three distinct subunits (alpha, beta, and gamma c) and regulates proliferation of T lymphocytes. Intracellular signalling results from ligand-mediated heterodimerization of the cytoplasmic domains of the beta and gamma c chains. To identify the residues of gamma c critical to this process, mutations were introduced into the cytoplasmic domain, and the effects on signalling were analyzed in the IL-2-dependent T-cell line CTLL2 and T-helper clone D10, using chimeric IL-2R chains that bind and are activated by granulocyte-macrophage colony-stimulating factor. Whereas previous studies of fibroblasts and transformed T cells have suggested that signalling by gamma c requires both membrane-proximal and C-terminal subdomains, our results for IL-2-dependent T cells demonstrate that the membrane-proximal 52 amino acids are sufficient to mediate a normal proliferative response, including induction of the proto-oncogenes c-myc and c-fos. Although gamma c is phosphorylated on tyrosine upon receptor activation and could potentially interact with downstream molecules containing SH2 domains, cytoplasmic tyrosine residues were dispensable for mitogenic signalling. However, deletion of a membrane-proximal region conserved among other cytokine receptors (cytoplasmic residues 5 to 37) or an adjacent region unique to gamma c (residues 40 to 52) abrogated functional interaction of the receptor chain with the tyrosine kinase Jak3. This correlated with a loss of all signalling events analyzed, including phosphorylation of the IL-2R beta-associated kinase Jak1, expression of c-myc and c-fos, and induction of the proliferative response. Thus, it appears in T cells that Jak3 is a critical mediator of mitogenic signaling by the gamma c chain. 相似文献
18.
Detection of autologous mixed lymphocyte reaction responding cells and their precursor frequency in NZB mice 总被引:1,自引:0,他引:1
The autologous mixed lymphocyte reaction (AMLR) can be detected in older NZB mice after treatment of the responding cell population with monoclonal anti-I-Ad and complement and supplementation of the culture medium with T-cell growth factor (TCGF) from young animals. The addition of TCGF to cultures containing responding cells alone that had not been pretreated with anti-I-A plus complement resulted in high levels of background proliferation. This is indicative of a high number of preexisting I-A-positive, activated, TCGF-responsive T cells in these mice. These activated cells could also be removed by treatment with anti-I-A antibody and panning on anti-mouse Ig plates, or by BUdR and light killing of those cells proliferating in the presence of TCGF or purified IL-2. Prior treatment of the responding cells with anti-Lyt 2 and complement did not effect the AMLR. An NZB AMLR responding cell line was established using these methods. This line retained haplotype specificity in a proliferation assay. Limiting dilution analysis of the precursor frequency of AMLR responding cells in the nonautoimmune C58 and BALB/C strains in culture medium with TCGF gave a frequency of between 1 in 35,000 and 1 in 88,000. In young, AMLR-positive, NZB mice, supplementation with TCGF yielded precursor frequencies within the normal range. In older NZB mice, the addition of TCGF resulted in increased background proliferation of preactivated, IA+ T cells. After removal of these cells with anti-I-A plus complement, AMLR responding cells were found at normal frequency levels when stimulated in the presence of TCGF. In the oldest animals tested (greater than 18–20 weeks), normal precursor frequencies could not be demonstrated even after this treatment, representing a true decline in the AMLR responding cell number. AMLR deficiency in NZB mice appears therefore to be the result of the combined effects of decreased lymphokine production, excessive T-cell activation, and finally decreased numbers of AMLR responding cells. 相似文献
19.
The 2H4 antigen, comprised of a 200/220-kDa glycoprotein of the leukocyte common antigen (LCA) family, is expressed on a suppressor inducer, but not a helper inducer subset of T4 cells. Earlier studies have demonstrated that the T4+2H4+ subset of cells maximally responded to the AMLR and this molecule has an important role in generated suppressor signals in AMLR/Con A-activated T cell systems. In the present study, we examined the effect of a series of monoclonal antibodies including anti-2H4 antibody on the initial activation of T4 cells in response to self-Ia antigens. We found that the addition of anti-2H4 antibody resulted in an augmentation of the proliferative response of T4 cells in AMLR, whereas other antibodies reactive with LCA/T200 antigens lacked this ability. Furthermore, anti-2H4 antibody enhanced both IL-2 production and IL-2R expression in this AMLR system. This enhancing effect was inhibited by anti-T3 antibody. Moreover, the suppressor inducer function of AMLR T4 cells was enhanced with anti-2H4 antibody by increasing the number of 2H4+ cells with high antigen density. Taken together, these results suggest that the 2H4 antigen may serve as an accessory structure for enhancing the activation of the T4+2H4+ suppressor inducer subset at initiation of cell triggering. 相似文献
20.
Suzuki N Nakatsuka H Mochizuki M Nishi N Kadoya Y Utani A Oishi S Fujii N Kleinman HK Nomizu M 《The Journal of biological chemistry》2003,278(46):45697-45705
Laminin alpha chains (alpha1-alpha5 chains) have diverse chain-specific biological functions. The LG4 modules of laminin alpha chains consist of a 14-stranded beta-sheet (A-N) sandwich structure. Several biologically active sequences have been identified in the connecting loop regions. Here, we evaluated the biological activities of the loop regions of the E and F strands in the LG4 modules using five homologous peptides from each of the mouse alpha chains (EF-1: DYATLQLQEGRLHFMFDLG, alpha1 chain 2747-2765; EF-2: DFGTVQLRNGFPFFSYDLG, alpha2 chain 2808-2826; EF-3: RDSFVALYLSEGHVIFALG, alpha3 chain 2266-2284; EF-4: DFMTLFLAHGRLVFMFNVG, alpha4 chain 1511-1529; EF-5: SPSLVLFLNHGHFVAQTEGP, alpha5 chain 3304-3323). These homologous peptides showed chain-specific cell attachment and neurite outgrowth activities. Well organized actin stress fibers and focal contacts with vinculin accumulation were observed in fibroblasts attached on EF-1, whereas fibroblasts on EF-2 and EF-4 showed filopodia with ruffling. Fibroblast attachment to EF-2 and EF-4 was mediated by syndecan-2. In contrast, EF-1 promoted alpha2beta1 integrin-mediated fibroblast attachment and inhibited fibroblast attachment to a recombinant laminin alpha1 chain LG4-5. The receptors for EF-3 and EF-5 are unknown. Further, when the active core sequence of EF-1 was cyclized, utilizing two additional cysteine residues at both the N and C termini through a disulfide bridge, the cyclic peptide significantly enhanced integrin-mediated cell attachment. These results indicate that integrin-mediated cell attachment to the EF-1 sequence is conformation-dependent and that the loop structure is important for the activity. The homologous peptides, which promote either integrin- or syndecan-mediated cell attachment, may be useful for understanding the cell type- and chain-specific biological activities of the laminins. 相似文献