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)

Human interferon-gamma (IFN-gamma) is an important immunomodulatory protein produced predominantly by T cells and large granular lymphocytes (LGLs). Whereas large amounts of data have been accumulated regarding IFN gamma gene expression in these two cell types, little information about IFN gamma expression in other cell types exists. In this study, we have analyzed the production of IFN gamma by the Epstein-Barr virus (EBV)-positive B-cell line, JLP(c), derived from a patient with Burkitt's lymphoma, and another human B-cell line, PA682BM-1, which was derived from an acquired immunodeficiency syndrome patient. Southern blot analysis indicates the presence of an Ig heavy chain gene rearrangement, but no rearrangement of the T-cell receptor beta chain gene or IFN gamma gene in these B-cell lines. Both cell lines were found to express surface IgD and other B-cell surface markers, thus confirming their B-cell lineage. Analysis for surface Ig, cytoplasmic Ig, and secreted Ig indicates that the two cell lines are in relatively early stages of the B-cell differentiation pathway. We now report that PA682BM-1 can be triggered by the protein kinase C (PKC) activators, phorbol 12-myristate 13-acetate (PMA) and (-)Indolactam-v, to secrete IFN gamma, whereas JLP(c) cells spontaneously produce low levels of IFN gamma that can be enhanced by PKC activators and interleukin-2 (IL-2). After activation of the cell lines with IL-2, (-)Indolactam-v, and PMA, increases in cytoplasmic messenger RNAs (mRNAs) of IFN gamma and the IL-2 receptor chains were also observed. The induction of IFN gamma mRNA and protein by IL-2 was completely blocked by a monoclonal antibody to IL-2 receptor p75 (beta chain), but not by the monoclonal antibody to p55 (alpha chain). Analysis of IFN gamma genomic DNA indicates that the gene is not amplified, but that hypomethylation in the 5' noncoding region of the IFN gamma gene has occurred in the B-cell line from the Burkitt's lymphoma patient that spontaneously produces IFN gamma. This finding suggests that the methylation state of the promoter region may play an important role in the control of IFN gamma gene expression in B cells.
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PMID:Interferon-gamma gene expression in human B-cell lines: induction by interleukin-2, protein kinase C activators, and possible effect of hypomethylation on gene regulation. 132 3

While recent studies in Rhesus monkeys have pointed out the importance of an intact nef gene for the development of acquired immunodeficiency syndrome (AIDS), no biological function has been so far unambiguously attributed to its product. Since Nef has been described to possess GTP-binding properties and to down-regulate CD4 cell surface expression, we looked for evidences of Nef interfering with the transduction of activating signals in human CD4+ T cells. We used a murine leukemia retroviral vector to express the HIV-1BRU nef gene in two permanent tumoral T-cell lines (CEM and Jurkat) and in two nonimmortalized, interleukin-2 (IL2)-dependent, T-cell clones. The single copy recombinant provirus integrated in the genome of these cells directed the synthesis of a 27-kD protein with a half-life greater than 5 h. The levels of expression of cell surface molecules involved in T-cell functions (CD4, CD3, CD28, CD29, IL-2 receptor) were not modified in cell populations expressing Nef. In immunocompetent T-cell clones, cell proliferation and lymphokine production in response to activating stimuli (IL-2, alloantigens, phorbol esters, or antibodies directed against CD2, CD3, CD4, CD28) remained unmodified. Moreover, the presence of Nef did not change the kinetics of human immunodeficiency virus (HIV) infection.
AIDS Res Hum Retroviruses 1992 May
PMID:Activation pathways and human immunodeficiency virus type 1 replication are not altered in CD4+ T cells expressing the nef protein. 135 46

Mycobacterium avium-intracellulare (MAI) is an ubiquitous soil contaminant that rarely causes disseminated disease in adults, regardless of immunological status. In AIDS patients, however, this microorganism invades virtually every tissue and organ, and most conventional chemotherapeutic agents are usually ineffective against MAI. We report here that monocytes, in which MAI has established an intracellular parasitic stage, appear to be under the control of natural killer (NK) cells. Autologous large granular lymphocytes (LGL), purified from human peripheral blood mononuclear cells (PBMC), were capable of efficiently lysing MAI-infected monocytes in a 5 hr 51Cr-release assay. More importantly, interleukin 2 (IL-2) was able to activate the LGL to a high degree of lysis of infected monocytes. Additionally, 3 to 4 days of incubation of LGL with MAI resulted in the induction of killer cells capable of killing bacterially-infected monocytes, as well as tumor cells. Northern blot analysis of RNA from MAI-stimulated LGL revealed specific messages for both IL-2 receptor proteins (p55 and p70). Thus, MAI can directly activate killer cells, which may therefore play a role in containment of MAI infection by lysis of parasitized monocytes before the bacteria can multiply and spread to other sites.
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PMID:Cytokine activation of killer cells in mycobacterial immunity. 141 86

Lung involvement in patients affected by HIV-1 infection is characterized by an alveolitis sustained by the accumulation of CD8+ T lymphocytes. To investigate whether in situ T cell growth plays a relevant role in the pooling of CD8+ lymphocytes, we have analyzed the activity of two lymphokines involved in the mechanisms of T cell proliferation, i.e., interleukin-2 (IL-2) and interleukin-4. To this aim, following appropriate triggering and blocking, the expression and the functional role of IL-2 receptors (IL-2R) (both p55 and p75 chains) and IL-4 receptors have been analyzed on T lymphocytes obtained from the bronchoalveolar lavage (BAL) of 16 HIV-1+ patients. Molecular and phenotypic studies we performed demonstrated that CD8+ lymphocytes from the BAL of HIV-1 + patients strongly expressed the p75 chain of IL-2 receptor, while neither p55 mRNA nor its surface membrane product (Tac antigen) was detectable; in addition, there was no expression of IL-4 receptors. IL-2 stimulation was able to induce T cell growth in a dose-dependent manner, whereas IL-4 did not. Finally, using mAbs which specifically block the p55 or p75 IL-2R, we showed that both subunits of IL-2R were involved in the proliferative activity of lung lymphocytes. The results obtained in the present study directly demonstrate that BAL T lymphocytes of HIV-1 + patients express a fully functional IL-2 receptor apparatus, pointing to the role for this lymphokine in maintaining the alveolitis taking place in the lungs of AIDS patients.
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PMID:Expression of a functional p75 interleukin-2 receptor on lung lymphocytes from patients with human immunodeficiency virus type 1 (HIV-1) infection. 143 Jan 8

Mycobacterium avium is an intracellular opportunistic pathogen commonly seen in AIDS patients. M. avium-infected monocytes have been recently shown to be lysed by interleukin-2 (IL-2)-activated killer cells. Since some bacterial products can directly augment natural killer activity, we examined the ability of these microorganisms to induce killer cell activity. Coculture of M. avium with large granular lymphocytes (LGL) was found to augment the ability of LGL to lyse both tumor cells and bacterially infected autologous monocytes. The induction of tumoricidal activity by M. avium was only partially neutralized by the presence of anti-IL-2 antibodies, indicating that both IL-2-dependent and IL-2-independent mechanisms are responsible for activation of killer cells. Furthermore, only the direct interaction between bacterium and LGL could induce the expression of both IL-2 receptor alpha protein and mRNA, an effect which was abrogated by the presence of genistein, a tyrosine kinase inhibitor. Thus, M. avium was seen to induce killer cells, an activity that is concomitant with the up-regulation of IL-2 receptor alpha, or Tac antigen, expression and which involves signal transduction mechanisms mediated by tyrosine kinase activity.
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PMID:Mycobacterial induction of activated killer cells: possible role of tyrosine kinase activity in interleukin-2 receptor alpha expression. 161 49

Lymphocyte activation induces production of soluble IL-2 receptor (sIL-2R) which is a large portion of the CD25 membrane molecule and which is detectable in serum. Serum sIL-2R is reported here to increase as a direct effect of the HIV infection and not to be due to secondary opportunistic infections. sIL-2R increased promptly after HIV seroconversion in 83% of 50 initially seronegative homosexual men. The sIL-2R serum levels stabilized in the third year after seroconversion and were then predictive of later CD4 T cell levels and development of AIDS. In two studies of 59 and 395 seropositive men, beta-2 microglobulin (B2M) and neopterin levels in serum correlated closely with each other but not with sIL-2R levels. Thus, increased production of sIL-2R may reflect pathological processes distinct from those determining B2M and neopterin increases. Membrane CD25 expression on peripheral blood lymphocytes, unexpectedly, was found to be decreased in HIV infection. This contrasted with the increased sIL-2R in serum. Investigations with sensitive flow cytometry technics showed that CD25 was expressed at reduced levels and averaged only 12% of lymphocytes from HIV-infected individuals in contrast to 25% in noninfected individuals. All major lymphoid populations showed reductions in CD25 positive cells. This reduction in lymphoid membrane CD25, however, was not inversely correlated with the increased serum levels of sIL-2R or with other parameters of immune deficiency or activation. Thus, surface CD25 loss and serum sIL-2R increase are separate and independent consequences of HIV infection.
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PMID:Serum increases and lymphoid cell surface losses of IL-2 receptor CD25 in HIV infection: distinctive parameters of HIV-induced change. 168 May 89

A monocytic cell line, THP-1, was acutely infected with HIV, and the effects of various factors including INF-gamma, LPS, IL-2, and IL-6 were analyzed. While IFN-gamma suppressed HIV production, IL-2 and IL-6 augmented it. The suppressive effect of IFN-gamma was not overcome by IL-2 or by LPS. We studied whether the induction of IL-2 receptor alpha (IL-2R alpha) expression by those factors was related to HIV infection or not. By immunofluorescence analysis using monoclonal anti-IL-2R alpha antibody, we observed that HIV infection itself induced IL-2R alpha expression moderately in U937 and THP-1, and IL-6 as well as IFN-gamma highly induced IL-2R alpha expression both in uninfected and infected THP-1. Although induction of HIV production and IL-2R alpha expression by cytokines seem not to be directly correlated, these results suggest that soluble IL-2R alpha increased in AIDS patients might be at least partly derived from infected monocyte/macrophages activated by various cytokines, especially IL-6, which is mainly produced by themselves.
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PMID:Effect of cytokines on HIV release and IL-2 receptor alpha expression in monocytic cell lines. 169 Dec 89

We and others have shown that several T cell responses induced by the mitogen phytohaemagglutinin (PHA), including T cell colony formation, IL-2 receptor (IL-2R) expression, and IL-2 production are impaired in patients with AIDS and lymphadenopathy syndrome (LAS). We investigated whether phorbol myristate acetate (PMA) could act in synergy with PHA (as it does in healthy subjects) to enhance in vitro T cell responses of patients at all stages of infection by HIV. In AIDS patients with opportunistic infections (AIDS/OI), PHA + IL-2 + PMA led to a total disappearance of T cell colonies in 10/11 patients, among whom six already displayed very low numbers of colonies induced by PHA + IL-2 (less than 50 colonies/5 x 10(4) cells). In contrast, T cell colony formation induced by PHA + IL-2 + PMA was maintained or increased, compared with that induced by PHA + IL-2, in five out of six AIDS patients with Kaposi's sarcoma (AIDS/KS), 10/14 LAS and six out of seven HIV-seropositive asymptomatic (HIV+/AS) homosexuals. In these three groups of patients, a low percentage of colony cells induced by PHA + IL-2 + PMA expressed CD3 and CD4 molecules, but 50-89% of cells were IL-2R (Tac) positive, as in healthy controls. Studies on T cell activation and IL-2 production were performed on a selected group of 12 HIV-infected patients for whom sufficient numbers of lymphocytes could be obtained. PMA induced CD4 down-modulation in controls and in HIV-infected patients. However, CD3 down-modulation and induction of the Tac chain of IL-2R by PMA were significantly impaired in patients, compared with controls, and these two parameters were correlated. Although PHA alone induced virtually normal levels of Tac antigen on patients' cells, Tac induction by PHA + PMA was significantly decreased in patients versus controls. Cells from five out of 10 patients tested failed to produce detectable amounts of IL-2 after PHA stimulation, whereas IL-2 production increased significantly in all patients tested (n = 9) after PHA + PMA, with a level of IL-2 activity significantly higher than in controls. No correlation was found in this group of patients between the effects of PMA + PHA on T cell colony formation, Tac expression, or IL-2 production, as compared with PHA alone. Taken together, our results indicate that in vitro T cell functional studies with PMA may be useful to evaluate better the defects of T cell activation in HIV-infected patients.
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PMID:Effect of phorbol myristate acetate on T cell colony formation, interleukin-2 (IL-2) receptor expression and IL-2 production by cells from patients at all stages of HIV infection. 169 61

Neopterin concentrations in body fluids of HIV-1 seropositives provide predictive information. In 1986, we examined serum and urine neopterin concentrations in 29 HIV-1 seropositives. Serum levels of soluble IL-2 receptor (sIL2R), soluble CD8 (sCD8), tumour necrosis factor alpha (TNF-alpha) and circulating immune complexes (CIC) were retrospectively analysed in 1989. All individuals had increased serum and urine neopterin, sIL2R and CIC concentrations, 27/29 had increased sCD8 concentrations, whereas all had normal TNF-alpha levels. During a 3-year follow-up, high urine and serum neopterin concentrations were significantly associated with progression to AIDS and with the occurrence of AIDS-associated death. Both neopterin variables were of similar predictive value (p less than 0.001, generalized Wilcoxon test). sIL2R concentrations were of borderline significance in predicting the onset of AIDS (p = 0.05). All other parameters lacked predictive information in our study. We conclude, that chronic immune activation is detectable in almost all HIV-1 seropositives. Chronic immune activation may be associated with HIV-1 replication and may contribute to the immunopathology of HIV-1 infection.
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PMID:Immune activation markers to predict AIDS and survival in HIV-1 seropositives. 212 76

Histamine inhibited the proliferative response of human peripheral blood mononuclear cells (PBMC) to the T cell mitogen Phytohemagglutinin-P (PHA-P) in a dose-dependent fashion. This inhibition was mediated via the H2 receptor since cimetidine, a known H2 antagonist, removed the inhibition, whereas the addition of the H1 antagonist Diphenhydramine did not. Inhibition occurred during the inductive phase of the cell cycle, since histamine added 24 hours after PHA-P stimulation had no effect on subsequent T cell proliferation, and was attributable to inhibition of interleukin-2 (IL-2) gene expression. Both secreted IL-2 and messenger RNA coding for IL-2 were inhibited by histamine. In contrast, histamine exerted no inhibitory effect on the expression of cell surface receptors for IL-2 as determined by flow cytometry. Furthermore, histamine-treated cells retained full responsiveness to exogenously administered IL-2, which completely reversed the anti-proliferative effect of histamine. In some donors, histamine enhanced the percentage of IL-2 receptor positive cells. Stimulated PBMC from AIDS KS patients as a group, displayed a lower percentage of IL-2 receptor bearing cells, which was significantly increased by the addition of histamine even at concentrations as low as 10(-6) M and peaking at 10(-3) M. These findings indicate that histamine exerts its anti-proliferative effects on T cells by inhibiting IL-2 production, via blockade of IL-2 gene expression. In addition, histamine seems to exert immunomodulating effects on IL-2 receptor expression, particularly in those individuals with AIDS-KS.
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PMID:Histamine blocks interleukin 2 (IL-2) gene expression and regulates IL-2 receptor expression. 226 28


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