Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previously, using flow cytometric resonance energy transfer and lateral diffusion measurements, we demonstrated that a 95-kDa protein identified by two monoclonal antibodies (OKT27 and OKT27b) interacts physically with the 55-kDa alpha protein of the high-affinity interleukin 2 (IL-2) receptor. In the present study, this 95-kDa protein (p95) was purified and amino acid sequence data were obtained that showed strong homology to the human intercellular adhesion molecule 1 (ICAM-1). The identity of the p95 protein with ICAM-1 was confirmed by sequential immunoprecipitations using OKT27 and an antibody, WEHI-CAM-1, that is directed toward ICAM-1. We confirmed the physical proximity of p95/ICAM-1 to the IL-2 receptor alpha subunit by demonstrating that radiolabeled IL-2 could be cross-linked to this protein expressed on activated T cells. In functional studies, the antibodies OKT27 and OKT27b inhibited T-cell proliferative responses to OKT3, to soluble antigen, and to heterologous cells (mixed lymphocyte reaction). However, these antibodies did not inhibit IL-2-induced proliferation of an IL-2-dependent T-cell line. Taken together with our previous observations, the present studies suggest that ICAM-1 is in proximity and interacts physically with the high-affinity IL-2 receptor. The association of ICAM-1 with the IL-2 receptor may facilitate the paracrine IL-2-mediated stimulation of T cells expressing IL-2 receptors by augmenting homotypic T-T-cell interaction, by receptor-directed focusing of IL-2 release by helper T cells, and by focusing IL-2 receptors of the physically linked cells to the site of lymphocyte function-associated antigen 1-ICAM-1-IL-2 receptor interaction.
Proc Natl Acad Sci U S A 1990 Sep
PMID:Association of intercellular adhesion molecule 1 with the multichain high-affinity interleukin 2 receptor. 197 56

Very Little is known about the immunological attributes of human endothelial cells. In this study, we performed immunologic phenotypic analysis of cultured human dermal microvascular endothelial cells in comparison with human umbilical vein endothelial cells and examined the ability of various biologic response modifiers to alter the phenotypes. Using FACS analysis, both types of the cells appear to lack many of the cell surface markers of immunologically proficient cells, E.G. OKT4, OKT8, Leu7, FcIgG receptor, complement receptors, IL-2 receptor and HLA-Dr, but they possess beta 2-microglobulin and DAF. HLA-Dr antigens can be induced on both types of endothelial cells by gamma-IFN in a dose and time dependent manner. Both types of endothelial cells possess several kinds of Cell Adhesion Molecules (CAMs), such as ICAM-1, CD44, LFA-3, but not LFA-1 or CD2. ICAM-1 but not LFA-3 or CD44 can be upregulated by exposure of both types of endothelial cells to gamma-IFN, IL-1 and TNF. These data suggest that endothelial cells of the dermal microvasculature may play central roles in a variety of different cutaneous inflammation.
Nihon Hifuka Gakkai Zasshi 1990 Sep
PMID:[Immunophenotypic analysis of human endothelial cells]. 197 95

The effect of the anti-rheumatic drug CCA (disodium 4-chloro-2,2'-iminodibenzoate) on the proliferation of T cells activated by PHA was examined. Cell cycle analysis showed that CCA blocked the transition of the cells from G1 to S (progression), but had little effect on the G0----G1 transition (initiation). CCA had no significant effect on IL-2 receptor expression, an early G1 event, but did inhibit transferrin receptor expression, a late G1 event. CCA did not inhibit IL-2 production by PHA-activated T cells, but did block IFN-gamma production at 72 hr after the stimulation. CCA failed to inhibit c-myc mRNA induction, but did delay the decrease in c-myc mRNA levels that normally occurs with the onset of DNA synthesis. These results indicate that CCA inhibits the progression, but not initiation, of human T cell proliferation.
Clin Immunol Immunopathol 1990 Sep
PMID:CCA (disodium 4-chloro-2,2'-iminodibenzoate) inhibits progression of human T cell proliferation triggered by PHA. 211 15

Infection of mice with lymphocytic choriomeningitis virus (LCMV) produces a rapidly induced immuno-suppression manifested by low lymphocyte proliferation in response to lipopolysaccharide (LPS) and concanavalin A (ConA). Analysis of the mechanisms underlying the unresponsiveness to these mitogens was undertaken at the cellular and molecular levels 7 days after infection. The selective elimination of CD8+ T cells and the results of coculture experiments demonstrated that unresponsiveness was not due to suppressor cells. Similarly, the role of inhibitory factors such as prostaglandins was excluded, since indomethacin, which inhibits their production, did not reverse the unresponsiveness. Analysis of different cytokines secreted by ConA-activated macrophages or T cells revealed that interleukin-1 (IL-1), synthesized during the T-dependent activation of macrophages by ConA, was normally produced by cells from LCMV-infected mice. In contrast, IL-2, which is produced by activated CD4+ T cells, was undetectable. Addition of exogenous IL-2 did not restore the proliferative response, although the p55-kilodalton protein of the IL-2 receptor was induced by ConA on CD4+ cells from LCMV-infected mice. Our results can be interpreted as showing that (i) unresponsiveness to mitogens of cells from LCMV-infected mice is not due to altered functions of the macrophages with respect to IL-1 production; (ii) CD4+ cells are activated, since the p55 chain of the IL-2 receptor is induced; (iii) the lack of IL-2 production cannot explain T-cell unresponsiveness, since addition of exogenous IL-2 did not restore the proliferative response. Taken together, these data suggest that T-lymphocyte unresponsiveness should be related to an inherent proliferative defect subsequent to T-cell activation and IL-2 receptor expression.
J Virol 1990 Sep
PMID:Lymphocytic choriomeningitis virus-induced immunodepression: inherent defect of B and T lymphocytes. 214 39

A 76-year-old woman developed angiosarcoma 11 years after a radical mastectomy in the chronic lymphedema of the ipsilateral arm, referred to as Stewart-Treves syndrome. The patient was treated by intravenous and intralesional injection of recombinant interleukin 2 (rIL-2; TGP-3, Takeda Chemical Industries, LTD, Osaka). Intralesional injection was more effective than systemic administration. After a month, the lesion where the local injection was done showed little tumor cells with a dense infiltrate composed of lymphoid cells. It was observed that NK activity, LAK activity and IL-2 receptor positive T-cells in the peripheral blood increased during the administration of rIL-2. As the lesion was too large to be treated with rIL-2 alone, radiotherapy was performed. But the patient had no remarkably improvement and died 16 months later from the onset. Immunotherapy with rIL-2 can be useful for angiosarcoma and more effective regimen of rIL-2 is a important problem.
Nihon Hifuka Gakkai Zasshi 1990 Sep
PMID:[A case of Stewart-Treves syndrome--treatment with recombinant interleukin 2 and a review of Japanese literature]. 226 96

Interleukin 2 (IL-2) is a potent growth factor for T lymphocytes, playing a crucial role in the immune response. In view of the considerable evidence that the immunoregulatory cytokines (or lymphokines) also play a role in the growth and differentiation of cells in the central nervous system (CNS), we examined the operation of the IL-2 system in a cell line of CNS origin by expressing a cDNA encoding the beta chain of the human IL-2 receptor (IL-2R beta, a 75-kDa protein). When the cDNA was expressed in a human oligodendroglioma cell line, ONS-21, the IL-2R beta bound IL-2 with an affinity similar to that in lymphoid cells (Kd, approximately 2 nM). Furthermore, cell proliferation ([3H]thymidine incorporation) was stimulated by IL-2. These results demonstrate that the same cytokine receptor is functional in cells of the immune system and CNS and point to a molecular mechanism that is similar for growth-signal transduction between lymphoid and neural cells but that may be different in other cells, such as fibroblasts.
Proc Natl Acad Sci U S A 1990 Sep
PMID:Interleukin 2 receptor beta chain expressed in an oligodendroglioma line binds interleukin 2 and delivers growth signal. 239 60

Blast formation and mitotic activation of G0-arrested mouse thymocytes were triggered by the addition of concanavalin A plus interleukin 2 (IL-2) to the culture medium. When added alone, Con A induces within 6 hr a complex reprogramming ("priming") that comprises the activation of the IL-2 receptor gene. The primed thymocytes are competent to interact with IL-2 and to respond to its growth-promoting effect, which corresponds to blast formation and mitotic activation. Cyclosporin A, an immunosuppressive cyclic peptide of fungal origin, prevents in T lymphocytes the activation of a set(s) of genes encoding lymphokines and the IL-2 receptor but does not affect their expression once they have been activated. The biomedical implications of these observations are discussed.
Proc Natl Acad Sci U S A 1986 Sep
PMID:Cyclosporin A prevents induction of the interleukin 2 receptor gene in cultured murine thymocytes. 242 33

The present study shows the in vitro effects of a novel immunosuppressive agent, FK506, in comparison with cyclosporin A (CsA). FK506 inhibited concanavalin A response and allo-mixed lymphocyte reaction of murine splenic lymphocytes in a dose-dependent manner, and at 40- to 200-fold lower concentrations than CsA. Allo-cytolytic T lymphocyte induction from murine thymocytes was also inhibited by FK506, whereas the ability of cytolytic T lymphocyte to lyse targets was not affected by the agent. Immunosuppressive effects of FK506 were further characterized by using antigen specific-proliferative T lymphocyte clones, BC.21 and KO.6. FK506 inhibited the proliferation of T cell clones stimulated with specific antigens in a dose-dependent manner, and at about 100-fold lower concentrations than CsA. However, cloned T cells, once activated, were scarcely affected by the agent; interleukin-2 (IL-2) driven proliferation of cloned T cells was not inhibited. On the other hand, it was found that FK506 inhibited both IL-2 secretion and IL-2 receptor expression of BC.21 after stimulation with the specific antigen. FK506 also inhibited the proliferation of BC.21 stimulated with phorbol 12-myristate 13-acetate plus calcium ionophore, indicating that it directly affected the signaling pathway downward from the perturbation of the Ti/T3 complex. Finally, it was suggested that FK506 and CsA synergistically inhibited the antigen-driven proliferation of cloned T cells. These results indicate that the novel immunosuppressive agent, FK506, affects T cell activation with mechanisms similar to those of CsA but at considerably lower concentrations.
J Immunol 1987 Sep 15
PMID:Novel immunosuppressive agent, FK506. In vitro effects on the cloned T cell activation. 244 55

The immuno-pharmacological profile of a novel immunosuppressive agent, FK-506 produced by a streptomycete, is presented here. We proceeded to test the effect of the agent on various in vitro immune systems. It showed that mixed lymphocyte reaction, cytotoxic T cell generation, the production of T cell-derived soluble mediators such as interleukin 2 (IL-2), interleukin 3 and gamma-interferon and the expression of the IL-2 receptor were suppressed by this agent. The IC50 values of FK-506 and ciclosporin (CS) in all tests were approximately 0.1 nM and 10 nM, respectively. Therefore, the novel agent, FK-506 suppressed in vitro immune systems at about hundred times lower concentration than CS.
J Antibiot (Tokyo) 1987 Sep
PMID:FK-506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK-506 in vitro. 244 22

The role of distinct regions of HLA class I molecules in regulating T-cell activation via the CD3-antigen receptor complex was investigated. Monoclonal antibodies (MoAbs) which recognize monomorphic and polymorphic epitopes on HLA Class I molecules were shown to inhibit T-cell proliferation to OKT3. These MoAbs have differential effects on the synthesis of interleukin-2 (IL-2) and IL-2 receptor expression. Cell cycle analysis demonstrated that these MoAbs function both in inhibiting cell cycle entry (G0-G1 shift) and in blocking cell cycle progression (G1-S shift) of activated T cells. Furthermore, these MoAbs have regulatory effects on the alternate pathway of T-cell activation via the CD2 molecule, T-cell activation induced by PHA, and activation induced by the phorbol ester PMA in conjunction with the calcium ionophore Ionomycin. Thus these MoAbs have different effects depending upon the pathway of T-cell activation. The results indicate that HLA class I molecules are selectively involved in the sequence of intracellular events leading to T-cell activation and proliferation.
Cell Immunol 1988 Sep
PMID:CD3 pathway of T-cell activation. II. Role of HLA-class I molecules in early events. 245 48


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