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

Selective congenital deficiency of the CD4 inducer T lymphocyte subset is a recently described variant of combined immunodeficiency. To further characterize the cellular and molecular mechanisms which lead to the profound T and B cell immunodeficiency in this condition, we examined in vitro immunoregulatory T lymphocyte activation and effector function, interleukin-2 (IL-2) synthesis, IL-2 receptor generation, and CD4 gene structure. Immunophenotyping of T lymphocytes demonstrated a selective deficiency of CD4+ cells, with normal numbers of CD2+ and CD3+ T cells, nearly all of which expressed the CD8+ determinant. Mitogen- and alloantigen-induced blastogenesis was profoundly decreased. B lymphocytes were present in normal numbers but there was a functional dysgammaglobulinemia (low IgG, normal IgM, low IgA) with no antibody response to in vivo immunization. T cells from the patient did not provide help to normal B cells for in vitro immunoglobulin synthesis; however, the patient's B cells were capable of synthesizing normal amounts of IgG when provided help from normal T cells. Concanavalin A failed to activate suppressor-inducer function in the patient's T cells. However, CD8+ T cell-mediated suppression was expressed if the patients T cells were cocultured with normal CD4+ T cells in a pokeweed mitogen-stimulated IgG secretion assay. IL-2 secretion and IL-2 receptor expression were both markedly reduced. Southern blot analysis of genomic DNA revealed no obvious abnormality in CD4 gene structure. The global defects in T cell activation, effector function, immunoregulation, and lymphokine generation observed in CD4+ inducer lymphocyte deficiency emphasizes the central role that the CD4 T lymphocyte plays in the activation and regulation in vivo immune responses.
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PMID:Combined immunodeficiency due to the selective absence of CD4 inducer T lymphocytes. 197 Dec 1

Stable transformants of the Jurkat T-cell line have been obtained that express either of two distinct forms of the type 1 human immunodeficiency virus nef gene: the nef-1-encoded protein (Nef-1) contains alanine, glycine, and valine at positions 15, 29, and 33, respectively; the protein specified by nef-2 (Nef-2) has threonine, arginine, and alanine at the corresponding positions. When Jurkat cells or their Nef-2-expressing transformants are treated with phorbol 12-myristate 13-acetate (PMA) plus either phytohemagglutinin (PHA) or antibodies against CD3 epsilon, T-cell receptor beta chain, or CD2, there is a prompt increase in interleukin 2 (IL-2) mRNA and intracellular calcium and in the IL-2 receptor alpha chain on the cell surface. Although cells expressing Nef-1 also induce calcium mobilization and the production of IL-2 receptor alpha chain, the formation of IL-2 mRNA is blocked in response to these stimuli. Moreover, Nef-1-expressing cells transfected with a plasmid in which the IL-2 promoter is fused to the chloramphenicol acetyltransferase (CAT) gene fail to induce CAT following treatment with PMA and PHA. By contrast, the parental and Nef-2-containing cells induce CAT normally. Nef-1-expressing cells can produce IL-2 mRNA in response to a combination of PMA and ionomycin, although much less efficiently than the parental Jurkat cells or Nef-2-expressing cells. These findings, and others described herein, suggest that the virally encoded Nef protein interferes with a signal emanating from the T-cell receptor complex that induces IL-2 gene transcription.
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PMID:Expression of the type 1 human immunodeficiency virus Nef protein in T cells prevents antigen receptor-mediated induction of interleukin 2 mRNA. 205 9

Envelope glycoprotein gp120 of human immunodeficiency virus type 1 (HIV-1) is known to inhibit T-cell function, but little is known about the mechanisms of this immunosuppression. Pretreatment of a CD4+ tetanus toxoid-specific T-cell clone with soluble gp120 was found to exert a dose-dependent inhibition of soluble antigen-driven or anti-CD3 monoclonal antibody-driven proliferative response, interleukin 2 (IL-2) production, and surface IL-2 receptor (IL-2R) alpha-chain expression, all of which were reversed by the addition of exogenous IL-2. mRNA for the gene encoding IL-2 was suppressed by treatment with gp120, but IL-2R gene transcription was not inhibited. Bypass activation of the T-cell clone with phorbol 12-myristate 13-acetate plus ionomycin was unaffected by gp120 pretreatment. Thus, gp120-CD4 interaction interferes with an essential role of the CD4 molecule in signal transduction through the CD3-antigen receptor (Ti) complex. Such a mechanism of gp120-induced immunosuppression, if operative in vivo, could contribute to the depressed specific immune responses associated with HIV infection.
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PMID:Human immunodeficiency virus type 1 envelope glycoprotein gp120 produces immune defects in CD4+ T lymphocytes by inhibiting interleukin 2 mRNA. 231 27

In this study we analyzed the ability of peripheral blood mononuclear cells (PBMC) from hemophilic patients (He) with negative or positive serology for the human immunodeficiency virus (HIV), to increase natural killer (NK) cytotoxicity upon stimulation with physiological and non physiological agents. Purified interleukin-2 (IL-2), the interferon (IFN)-inducer polyinosinic polycytidylic acid (PIC), recombinant alpha- and gamma-IFN and the protein kinase activator phorbol myristate acetate (PMA) were used as stimulatory agents. The NK functional response was correlated with the presence of PBMC bearing phenotypic markers of activated cells (IL-2 receptor, IL-2R) and of different NK cell maturation stages. Our results demonstrate that NK effector cells with slight lytic activity (Leu 7+ CD16-) predominated in HIV+ He patients. On the other hand the occurrence of IL-2R positive cells was similarly high in both HIV+ and HIV- individuals and was probably more related to chronic replacement treatment with Factor VIII or Factor IX concentrates than to HIV infection. The ability to respond to physiological NK regulators such as IL-2 and IFNs, or to the IFN-inducer PIC was impaired in HIV+ He, especially in HIV+ LAS individuals, suggesting that the inability of these cells to increase NK cell activity after appropriate induction was due to an intrinsic defect. Since phosphoinositide turnover and subsequent protein kinase C activation are thought to be part of the physiological mechanism of NK cytotoxicity, we studied the effect of PMA on PBMC from each group of patients. The ability to respond to PMA was lost only in PBMC from HIV+ LAS patients, indicating that impairment of the NK lytic mechanism progresses as the disease gets worse.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HIV infection and natural killer cytotoxicity in hemophilic patients. 238 63

The human immunodeficiency virus type I (HIV-1) possesses powerful regulatory elements that control the rate of replication of HIV-1 and subsequent processing of HIV-1 genes. We have used this regulatory mechanism to drive expression of foreign genes inserted in retrovirus vectors. This approach was used to express the human IL-2 gene in IL-2-dependent mouse CTLL-2 cells to determine the role of autonomous growth in maintaining proliferation of virus-infected T lymphocytes during HTLV-1-induced adult T-cell leukemia (ATL). Expression of IL-2 sequences in IL-2-dependent mouse CTLL-2 cells resulted in autonomous growth of IL-2-independent CTLL-2 clones. Endogenous expression of IL-2 appeared to interrupt normal constraints of growth in that these IL-2-independent clones showed reduced cell-density-dependent inhibition but not a tumorigenic phenotype. IL-2-independent CTLL-2 clones did not secrete detectable quantities of IL-2 into culture supernatant and exhibited reduced sensitivity to the inhibitory effects of both IL-2 and IL-2 receptor antibody. These results suggest that the IL-2 autocrine loop within these cells involves intracellular IL-2/IL-2 receptor binding. The apparent lack of IL-2 production and poor responsiveness to IL-2 or IL-2 antibodies displayed by cell lines from ATL patients may be explained by an intracellular IL-2/IL-2 receptor autocrine loop.
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PMID:Autonomous growth of lymphoid cells following IL-2 expression from retrovirus vectors containing HIV-1 trans-acting elements. 240 56

Transcriptional activation of the human interleukin-2 (IL-2) gene, like induction of the IL-2 receptor alpha (IL-2R alpha) gene and the type 1 human immunodeficiency virus (HIV-1), is shown to be modulated by a kappa B-like enhancer element. Mutation of a kappa B core sequence identified in the IL-2 promoter (-206 to -195) partially inhibits both mitogen- and HTLV-I Tax-mediated activation of this transcription unit and blocks the specific binding of two inducible cellular factors. These kappa B-specific proteins (80 to 90 and 50 to 55 kilodaltons) similarly interact with the functional kappa B enhancer present in the IL-2R alpha promoter. These data suggest that these kappa B-specific proteins have a role in the coordinate regulation of this growth factor-growth factor receptor gene system that controls T cell proliferation.
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PMID:Kappa B-specific DNA binding proteins: role in the regulation of human interleukin-2 gene expression. 249 18

Serum and cerebrospinal fluid (CSF) levels of interleukin-2 (IL-2), soluble IL-2 receptor (sIL-2R), and gamma-interferon (gamma-IFN) were measured in multiple sclerosis (MS) patients, human immunodeficiency virus type 1 (HIV-1)-infected patients and normal controls (NC). Increased levels of both IL-2 and sIL-2R were found in MS serum. Moreover, 11 of 50 MS patients showed detectable levels of IL-2 in the CSF. HIV-1-infected patients had increased levels of sIL-2R in serum and, less frequently, in the CSF. gamma-IFN was never detected in serum and CSF of all the patients studied. These findings confirm preliminary reports, further stress a systemic T-cell activation in MS, and support the hypothesis that an immunologic disorder exists in such patients.
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PMID:Immune activation in multiple sclerosis: study of IL-2, sIL-2R, and gamma-IFN levels in serum and cerebrospinal fluid. 250 88

Zidovudine (ZDV), an anti-human immunodeficiency virus (HIV) therapy, has been associated with reduction in mortality and improvement of patients with acquired immunodeficiency syndrome (AIDS). The ZDV recipients, however, experience a multitude of side effects of which bone marrow suppression is the most noteworthy, especially among patients with low CD4 cell counts. The effect of ZDV and interleukin-2 (IL-2) on phytohemagglutinin (PHA)-induced proliferative response of peripheral blood mononuclear cells (PBMs) from patients with HIV infection was investigated. ZDV 0.5 micrograms inhibited 40% of PHA-induced thymidine uptake in PBMs from healthy donors or patients with HIV, irrespective of their CD4 cell counts. However, IL-2 (10 U/ml) had differential effect on PHA-induced thymidine uptake that appeared to be dependent on absolute CD4 cell counts. While PBMs from patients with CD4 cell counts of 400/mm3 or more did not respond to IL-2 (low responders), IL-2 enhanced the PHA-induced thymidine uptake in PBMs from patients with CD4 cell counts less than 400/mm3 at an average of 60% (high responders). Moreover, IL-2 restored the ZDV-induced inhibition by almost 100% in the high responder group while it did not affect counts in the low responder group. The production of IL-2 in vitro, in response to PHA or recall antigens, was equivalently inhibited in both groups. These data suggest that ZDV and IL-2 could have an additive effect on immune parameters in certain groups of patients infected with HIV. The differential effect of IL-2 was independent of IL-2 receptor expression.
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PMID:Differential reconstitution of zidovudine-induced inhibition of mitogenic responses by interleukin-2 in peripheral blood mononuclear cells from patients with human immunodeficiency virus infection. 254 65

A previously described patient with X-linked agammaglobulinemia and growth hormone deficiency developed an echovirus-associated meningoencephalitis and dermatomyositis-like syndrome while being treated with intramuscular gamma globulin and human growth hormone. Initiation of high-dose intravenous gamma globulin resulted in resolution of the clinical symptoms and the patient has remained asymptomatic over the past 55 months. Lymphocyte phenotype analysis at the time of presentation with echovirus infection revealed an increase in CD2+, CD16+, HNK-1+ lymphocytes, a decrease in CD4+ T cells as well as absence of B cells. This elevation in the LGL/NK phenotype resolved with clinical improvement. In addition, there was evidence of lymphocyte activation following the development of echovirus infection (increase in HLA-DR expression and elevated serum IL-2 receptor levels) which resolved with clinical improvement. A muscle biopsy obtained during the period of the dermatomyositis-like syndrome demonstrated a CD8+ lymphocytic infiltrate very similar to the observations in classical dermatomyositis. Taken together, these findings suggest that growth hormone therapy in this patient failed to alter the humoral immunodeficiency. In addition, serum IL-2 receptor levels and lymphocyte phenotyping may be useful adjuncts for monitoring echovirus disease in immunodeficient patients.
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PMID:Lymphocyte analysis in a patient with X-linked agammaglobulinemia and isolated growth hormone deficiency after development of echovirus dermatomyositis and meningoencephalitis. 275 12

Uncertainty has existed as to whether a T-cell deficiency exists in human immunodeficiency virus (HIV) infection different from that inherent in the reduced T-cell numbers characteristic of the disease. Heretofore, methods for measuring T-cell responses in patients have been carried out with systems requiring monocytes as accessory cells. In the presence of high concentrations of interleukin-2, however, highly purified T cells respond in a monocyte-independent fashion to antibody reactive with the CD3 component of the antigen receptor complex Ti/CD3. Highly purified T cells of HIV-infected patients responded subnormally in this anti-CD3/IL-2 system, even in the case of patients who were asymptomatic or had only lymphadenopathy. The defective T-cell responses occurred over a wide range of concentrations of the anti-CD3. Neither poor IL-2 receptor function as reflected by responses to limiting dilutions of IL-2 nor IL-1 receptor function as defined by incremental proliferation when IL-1 is added accounted for this defect, which also correlated poorly with T4 and T8 numbers. These results suggested that the T-cell abnormality was closely related to Ti/CD3 function, was not specifically or restrictively associated with T4 cells, and was not due to defective IL-2- or IL-1-receptor functions. The amount of HIV RNA in 10(5) T lymphocytes from the patients amounted to less than that found in one cell of a standard HIV infected laboratory cell line (CEM), using slot-blot hybridization. Thus the T-cell deficiency we have observed was not likely to be due directly to cell killing by HIV resident in the T4 cells. Other factors may be important in inducing the immunodeficiency, some of which are discussed.
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PMID:Impairment in T-lymphocyte responses during early infection with the human immunodeficiency virus. 278 31


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