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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The biological significance of the signals triggered by the interaction of cell surface expressed LFA-1 and ICAM-1 has been investigated in Con A and immobilized anti-CD3 mAb stimulated cultures. When added at the beginning of activation in the presence of Con A, soluble anti-LFA-1 and anti-ICAM-1 mAbs could strongly inhibit cell proliferation. Such inhibitory effect was also exhibited in the proliferative response of thymocytes to immobilized anti-CD 3 mAb activation. However, the soluble anti-LFA-1 mAb was unable to inhibit the proliferation of primed thymocytes preactivated with Con A for 24 h or of IL-1 + IL-2 activated fresh thymocytes. Anti-LFA-1 mAb could profoundly inhibit Con A-induced thymocytes to produce IL-2 and IL-6 and to reduce IL-2 receptor expression. By contrast, anti-LFA-immobilized on plastic plates together with immobilized anti-CD 3 mAbs or CD 3 cross-linking with LFA-1 by secondary antibodies resulted in an enhanced activation signals for thymocytes to proliferate compared with that activated by anti-CD 3 alone. Thus, mAb to LFA-1 is a functional molecule for thymocyte activation, mediating signals contributed to very early phases of signal transduction through TCR/CD 3 pathway, and that LFA-1 might provide a costimulatory signal for expression of IL-2 R and IL-2 production.
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PMID:[Functional roles of LFA-1 involved in signal transduction for thymocyte activation]. 787 72

We have previously established conditions under which murine yolk sac cells can be maintained in vitro in the absence of thymus, and we reported that a spontaneously transformed Thy1.2+ yolk sac cell line was obtained after long term culture in vitro. We now provide further phenotypic characterization of a clone, YSA1, of this Thy1.2+ cell line showing that it expresses Thy1.2, CD3/TCR V beta 8, IL-2 receptor (IL2R), and heat stable antigen (HSAg), but does not express CD4/CD8 or TCR gamma delta. The YSA1 clone is an immature cell as indicated by the expression of IL2R and HSAg and by nonproduction of IL-2 upon stimulation by anti-CD3 antibody. The data show that yolk sac stem cells can differentiate into CD3/TCR expressing cells in the absence of thymus, but do not progress in vitro paralleling observations made on freshly-isolated yolk sac stem cells.
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PMID:A cloned lymphoid Thy1+ tumor line derived from murine yolk sac cells maintained in long-term cell culture in the absence of a thymic microenvironment expresses an unusual cell surface phenotype. 790 86

In C57BL/6 mice transgenic for a rearranged gene encoding a V beta 5+ beta-chain of the TCR, transgene expression among CD4+ cells decreases with age, such that approximately 40% of CD4+ cells express an endogenous beta-chain gene in 8-mo-old mice. A similar deletion of V beta 5+ cells is observed among CD4+ cells from nontransgenic littermates. V beta 5+ T cells are deleted intrathymically in I-E+Mtv-9+ strains of mice, but this chronic deletion occurs in the lymphoid periphery, in the absence of I-E. We now demonstrate the increased expression of the activation markers CD44 and VLA-4 among CD4+V beta 5+ cells, in the absence of either an increase in size or IL-2 receptor expression. Functional as well as phenotypic differences distinguish CD4+ from CD8+ cells in older V beta 5+ transgenic mice. Relative to their CD8+ counterparts, CD4+V beta 5+ cells are hyporesponsive to plate-bound anti-V beta 5 Abs, and this anergy is partially reversible by the addition of exogenous IL-2. These data suggest the deletion of CD4+V beta 5+ cells is the result of a process that includes their activation, loss of function, and their eventual removal. To investigate the involvement of the principal V beta 5 superantigen Mtv-9 in this chronic deletion, we have derived several lines of V beta 5+I-E-Mtv-9- mice. Transgene expression also declines with age in CD4+ T cells in these mice, clearly demonstrating that the chronic deletion of CD4+V beta 5+ cells does not require Mtv-9. There is considerable variation in the kinetics and efficiency of CD4+V beta 5+ deletion between lines of Mtv-9- transgenic mice that is not from differences in the profiles of endogenous mammary tumor proviruses nor readily explained by environmental differences that influence proviral expression. These results suggest the existence of genetic factors other than mammary tumor proviruses that influence the deletion of CD4+V beta 5+ cells in the absence of I-E.
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PMID:The induction of peripheral tolerance by the chronic activation and deletion of CD4+V beta 5+ cells. 790 16

1. The purpose of these studies was to characterize further previous observations from our laboratory indicating that physiologic concentrations of dexamethasone (DEX) and prostaglandin E2 (PGE2) added together result in synergistic inhibition of the proliferative response of T cells stimulated via the T-cell receptor CD3 signaling complex (TCR/CD3). 2. Various physiologic concentrations of DEX and PGE2 were added to T cells stimulated with immobilized anti-CD3 monoclonal antibody (mAb) and cultured at optimal and suboptimal cell densities. The results demonstrate that the proliferative response of anti-CD3 mAb-stimulated T cells cultured at a suboptimal cell density is more suppressed than that of T cells cultured at optimal concentrations. 3. The proliferative response of CD4+ T cells to immobilized anti-CD3 mAb was also determined in the presence of PGE2 and DEX. The data indicate that the CD4+ subset of T cells is more sensitive to the synergistic antiproliferative effects of DEX and PGE2 compared to whole T-cell populations. 4. Various concentrations of DEX and/or PGE2 were added to T cells stimulated with anti-CD3 mAb and the secretion of interleukin-2 (IL-2) was determined. The results demonstrate that concentrations of DEX and PGE2 which individually do not significantly suppress IL-2 synthesis act together to inhibit the synthesis of IL-2 synergistically. 5. The addition of an exogenous source of recombinant IL-2 (rIL-2) to T cells stimulated in the presence of DEX and PGE2 completely reversed the synergistic antiproliferative effect of these two compounds. This reversal was even more pronounced with T cells cultured at a suboptimal cell density. Additionally, PGE2 and DEX did not affect expression of the IL-2 receptor (IL-2R), as measured by upregulation of the alpha chain, on anti-CD3 mAb stimulated T cells. 6. Collectively these data indicate that physiologic concentrations of PGE2 and DEX, which alone have no effect on anti-CD3 mAb-induced T-cell proliferation, act synergistically to inhibit T-cell proliferation as well as IL-2 synthesis.
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PMID:Inhibition of anti-CD3 monoclonal antibody-induced T-cell proliferation and interleukin-2 secretion by physiologic combinations of dexamethasone and prostaglandin E2. 791 Jul 81

Female predominance of autoimmune diseases is widely known in humans and animals. To elucidate one of the underlying mechanisms, we examined whether sex differences exist at the level of extrathymic T cells in various organs of mice under physiological conditions. This attempt came from previous experimental results showing that estrogen administration to mice activates extrathymic T cells in the liver. Extrathymic T cells expressing TCR (and CD3) of intermediate intensity (i.e., intermediate TCR cells) and a high level of IL-2 receptor beta-chain (IL-2R beta), and thymus-derived T cells expressing TCR of bright intensity (i.e., bright TCR cells) and lacking IL-2R beta, were identified by immunofluorescent tests using mAbs. Three groups of different strains were examined. It was demonstrated that intermediate TCR cells were much more predominant in the liver and some other organs tested of female mice than of male mice, of each strain tested.
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PMID:Female predominance of extrathymic T cells in mice: statistical analysis. 803 41

The TCR/CD3 receptor complex plays a key role in antigen recognition and T-cell activation. Therefore, the present study investigates TCR alpha/beta (TCR1) and CD3 receptor density (RD, number of receptors per cell) on uremic helper-inducer (CD4) T lymphocytes in relation to T-cell proliferative response induced by anti-CD3 monoclonal antibodies (mAb). We found, that: (1) the number of TCR/CD3 receptors on uremic helper-inducer (CD4) T lymphocytes is decreased and correlated well with the blunted lymphocyte proliferation induced by anti-CD3 mAb; (2) these findings were associated with diminished binding capacity of IL-1 beta and IL-6 to their receptors (IL-1R, IL-6R) on helper-inducer T cells, whereas (3) the IL-2 receptor (IL-2R) and molecule expression of CD4 and lymphocyte function antigen-1 (LFA-1) were increased, and (4) uremic monocytes displayed a decreased density of intercellular adhesion molecule-1 (ICAM-1) expression, which interacts as receptor-ligand pair with LFA-1. The incubation of uremic and control peripheral blood mononuclear cells with uremic serum enhanced these above-mentioned changes in the expression of examined receptors and molecules. These data might also support the hypothesis that the blunted T-cell response to antigen in uremia is due to downregulation of the TCR/CD3 receptor complex by uremic milieu.
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PMID:Signalling via the TCR/CD3 antigen receptor complex in uremia is limited by the receptors number. 810 78

CD30 has been extensively studied as a cell surface marker expressed by Reed-Sternberg cells of Hodgkin's disease and other hematologic malignancies, although little is known about its expression by normal lymphoid cells. We therefore characterized the requirements for the induction of CD30 expression and identified the subsets of T cells that express CD30. CD30 is inducible on approximately 15% of normal PBMC stimulated with any of a variety of nonspecific T cell activators, including PHA, Con A, anti-T11(2) + T11(3), and anti-CD3; ionomycin alone induced lower percentages of CD30+ T cells (3 +/- 2%) compared to other stimuli. Maximal numbers of CD30+ cells were observed at 48 to 72 h of activation and the addition of rIL-2 did not affect these kinetics. However, CD30 expression was enhanced by the addition of exogenous rIL-2 to any of the stimuli tested, although rIL-2 alone did not lead to CD30 expression. The induction of CD30 during anti-CD3 mitogenesis was completely inhibitable by anti-IL-2 antibodies and partially inhibitable by rIL-4, indicating a requirement for both TCR triggering and IL-2 for its expression. Dual immunofluorescence analysis revealed that CD30+ cells were confined to CD3+ T cells that coexpressed higher levels of the p55 IL-2 receptor (CD25) than the CD30- population. Furthermore, CD30 expression was restricted to a subset of cells derived from CD45RO+ T cell precursors. Cell cycle analysis showed that CD30+ expression was not cell cycle dependent. Cross-linking of membrane CD30 induced Ca2+ in TCR+, but not TCR- Jurkat T cells. These results demonstrate that CD30 can serve as a T cell signal-transducing molecule and expressed by a unique subset of activated CD45RO+ T cells.
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PMID:CD30 is a signal-transducing molecule that defines a subset of human activated CD45RO+ T cells. 810 64

Rapamycin (RAPA) is a potent immunosuppressant. In this study we investigated the effect of RAPA on T cell proliferation triggered by various stimuli in an in vitro human model. The proliferation of T cells stimulated via an alternative pathway using phorbol myristate acetate (PMA) and anti-CD28 antibody (alpha CD28) in the absence of antigen-presenting cells (APC) was strongly inhibited by RAPA. T cell proliferation provoked via a combination of CD3/TCR and CD28 pathways using anti-CD3 antibody (alpha CD3) plus alpha CD28 was also inhibited by RAPA in the presence of APC. The mitogen (phytohaemagglutinin (PHA) or alpha CD3)-induced up-regulation of expression of the IL-2 receptor alpha chain (IL-2R alpha) and the IL-4 receptor (IL-4R) was sensitive to RAPA. This suggests that RAPA's interference with the IL-2 and IL-4 autocrine loops during T cell activation might contribute to RAPA's overall immunosuppressive effect. We have further demonstrated in a two-stage culture system that RAPA strongly inhibited IL-4-stimulated proliferation of T cells, the latter being either pretreated with alpha CD3 in the presence of APC, or with PMA plus alpha CD28 in the absence of APC. The result suggests that the Ca++ influx during the pretreatment is not obligatory for T cells to achieve IL-4 responsiveness. The results also indicate that RAPA's antiproliferative effect on IL-4-stimulated T cells is not contingent on the various mechanisms of cell priming. Therefore, RAPA's major target is probably at the second stage after the priming. Our study has extended current knowledge about the effect of RAPA on human T cells.
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PMID:Anti-CD28 antibody- and IL-4-induced human T cell proliferation is sensitive to rapamycin. 822 29

Extrathymic T cells in the hepatic sinusoids and intraepithelial lymphocytes (IEL) in the intestine of mice have both similar and different properties. In this study, both types of extrathymic T cells in mice were further characterized. Lymphocytes obtained from systemic immune organs, including the lamina propria and Peyer's patches, were also compared. Extrathymic T cells in both the liver and the intestine contained a large proportion of gamma delta T cells and expressed the alpha alpha homodimer of CD8. They became more prominent in athymic nude mice and in normal mice with aging, while disappearing in scid mice. Extrathymic T cells in the liver, on the other hand, had TCR of intermediate intensity (i.e., intermediate TCR cells) and IL-2 receptor beta-chains (IL-2R beta) of high intensity, similar to NK cells, whereas IEL had TCR of bright intensity and consisted of cells with both low and high levels of IL-2R beta. Thymus-derived T cells did not express IL-2R beta at all, at least at their resting conditions. Intermediate TCR cells included double-negative CD4-8- cells as well as single-positive cells. In contrast, IEL contained both double-positive (DP) CD4+8+ cells and single-positive cells. More precisely, IEL gamma delta T cells were mainly IL-2R beta + and single-positive (mainly CD8+), while IEL alpha beta T cells were mainly IL-2R beta- and contained both DP CD4+8+ cells and single-positive cells. CD4+ cells were more predominant than CD8+ cells in the liver, while CD8+ cells were overwhelmingly predominant in the intestine. These results suggest that both intermediate TCR cells and IEL are generated as primitive T cells in phylogeny, but later develop along independent pathways at their respective sites.
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PMID:Similarities and differences between extrathymic T cells residing in mouse liver and intestine. 828 93

We previously demonstrated that T cells with intermediate TCR intensity (i.e., intermediate TCR cells) which possibly generate extrathymically are preferentially present in the liver of mice. This population was further characterized with respect to the expression of IL-2 receptor (IL-2R) and others. Two-color staining for CD3 (or TCR alpha beta) and IL-2R alpha (and beta) demonstrated that intermediate TCR cells as well as NK cells constitutively expressed IL-2R beta but not IL-2R alpha. A small number of intermediate TCR cells was also identified in other immune organs by using this staining method. In vivo and in vitro stimulation experiments revealed that regular, bright TCR cells, which originally lacked the expression of both IL-2R alpha and beta, acquired the highest expression of IL-2R alpha and beta, while intermediate TCR cells did not. These results suggested, in conjunction with their other properties demonstrated here, that intermediate TCR cells might be more primitive T cells than regular T cells of thymic origin.
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PMID:Characterization of intermediate TCR cells in the liver of mice with respect to their unique IL-2R expression. 833 Mar 13


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