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)

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

HIV infection induces both immune deficiency and immune stimulation. Central to the pathology of HIV infection is reduction in the numbers and function of CD4 T cells. Impaired functions include decreased proliferation, IL-2 receptor expression and production of lymphokines (IL-2 and gamma interferon (IFN]. HIV infection stimulates B cells and CD8 T cells. This is seen relatively soon after HIV infection. Increased activation and immaturity are seen in both these cell groups. In vitro studies confirm HIV stimulation of these cells. Studies have been conducted on patients with AIDS and opportunistic infection (OI) or Kaposi's sarcoma (KS), with AIDS-related complex (ARC) or with persistent generalized lymphadenopathy (PGL), as well as on asymptomatic HIV-seropositive and -seronegative homosexually active men. The latter group has been followed at 6-month intervals for the past 2-3 years. Those who seroconverted (became HIV-infected) were studied to investigate early changes following HIV infection. To delineate the immunopathology of infection with HIV, serial testing of seropositive individuals was carried out to determine the rate of CD4-T-cell reduction. Lowered CD4-T-cell number and percentage and CD4/CD8 ratio correlate with the occurrence of AIDS and with survival after AIDS-KS diagnosis. Seropositive individuals, however, differed markedly in the rate of CD4-T-cell reduction; in some, no reduction in CD4 cells occurred over a two-year period of observation. We propose that, in individuals in which CD4 levels have reached a plateau, effective host resistance to further CD4 cytoreduction has occurred.
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PMID:Immune pathogenesis of AIDS and related syndromes. 295 95

In order to investigate the nature of the T cell defect associated with the acquired immune deficiency syndrome (AIDS) we studied the ability of peripheral blood mononuclear cells from 8 patients with Kaposi's sarcoma (KS), 2 with opportunistic infection (OI), 23 with AIDS-related symptoms complex (ARC) without KS or OI (ARC), and 29 heterosexual controls to produce interleukin II (IL-2) on phytohemagglutinin (PHA) stimulation and to respond to exogenously supplied IL-2. Patients with AIDS as well as those with ARC produced adequate levels of IL-2 in response to lectin stimulation when compared to controls (AIDS, 3.07 +/- 1.98 units; ARC, 3.03 +/- 1.89 units; controls, 3.75 +/- 1.52 units). However, the ability of these patients' cells to respond in vitro to exogenously supplied IL-2 as measured on short-term PHA-stimulated T cell blasts, was found to be severely impaired in patients with AIDS and ARC (AIDS, 22.4 +/- 6.0 X 10(-3) cpm; ARC, 20.1 +/- 4.2 X 10(-3) cpm; control, 41.4 +/- 4.2 X 10(-3) cpm). This impairment was associated with diminished expression of the IL-2 receptor on 7-day-old lectin-stimulated T cells from both patient groups (AIDS, 17.7 +/- 5.7; ARC, 36.8 +/- 4.4; control 71.8 +/- 1.7). These results should be considered when IL-2 is proposed as potential therapy in the treatment of AIDS. They also suggest that the nature of the AIDS defect is related to impaired hormone receptor expression.
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PMID:IL-2 production and response in vitro by the leukocytes of patients with acquired immune deficiency syndrome. 298 24

Retinoids have anti-tumor activity in several malignant and premalignant conditions. Since Kaposi's sarcoma is regulated by steroid hormones both in vivo and in vitro, we hypothesized that retinoids may have anti-tumor effects in AIDS-related Kaposi's sarcoma. Thus, 27 patients with mucocutaneous, non-visceral AIDS-related Kaposi's sarcoma were treated with all-trans retinoic acid (tRA). Poor tolerance was observed at the initial starting dose of 150 mg/m2, and thus subsequent patients were treated using a weekly dose escalation, starting with 45 mg/m2 (given daily, in subdivided doses), to the target dose of 150 mg/m2 (given daily in three subdivided doses). Nearly half (46%) of the patients had extensive mucocutaneous disease with over 25 lesions. No patient had received prior cytotoxic chemotherapy. Ten patients had CD4 lymphocytes of 200/mm3 or greater (strata I); and 17 had under 200/mm3 CD4 lymphocytes (strata II). The median of the average daily tRA dose administered was 150 mg (90 mg/m2; there was no significant difference in the dose tolerance between the two strata). Adverse effects consisted of transient mild to moderate headaches in 65% of patients, mild to moderate skin dryness and cheilitis in 61%, and nausea and vomiting in 31%. Hematologic toxicities included hypertriglyceridemia in 62%, anemia in 23%, and neutropenia in 23%. Partial response to therapy was observed in 4/24 (17%) evaluable patients, occurring after 12, 20, 24, and 28 weeks of therapy, and lasting 4-24 weeks. Three responders had baseline CD4 lymphocyte counts < 200/mm3. Three additional patients experienced reduction in measured indicator lesions of greater than 25% but less than 50%, and seven patients experienced disease stabilization of 16 weeks or greater. In evaluable patients, the median time to disease progression was 22 weeks and the overall median survival in all patients was 27.3 months. No significant changes in CD4 lymphocyte counts, p24 antigen, and beta 2 microglobulin were observed over time. However, a statistically significant increase was observed in soluble IL-2 receptor levels while on tRA (p = 0.037). We conclude that tRA has activity in patients with mucocutaneous AIDS-related Kaposi's sarcoma with acceptable toxicity. tRA has immunological effects without upregulation of HIV parameters. Additional studies in combinations or with more active retinoids are warranted.
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PMID:All-trans retinoic acid for the treatment of AIDS-related Kaposi's sarcoma: results of a pilot phase II study. 780 21

Kaposi's sarcoma (KS) is the most frequent neoplastic complication observed in HIV-infected patients. Cutaneous KS is the most common manifestation but visceral and lymph node involvement may occur. HIV-infection does not only lead to a decrease of certain cell types (CD4 T-lymphocytes), but also modifies the function of non-infected cells such as B-lymphocytes and NK-cells by upregulating cytokine release of IL-1, IL-6, GM-CSF, IFN-gamma and TNF-alpha. These multifunctional mediators show both autocrine and paracrine proliferative effects on normal endothelial cells and AIDS-related KS-cells. Using ELISA-, RIA- and IRMA-techniques we analysed the influence of seven cytokines (IL-1beta, IL-6, TNF-alpha, GM-CSF, IFN-alpha, IFN-beta, IFN-gamma) and the soluble IL-2 receptor (sIL-2R) on the growth of eight different KS-derived cell lines compared with eight fibroblast cell lines, established from skin biopsies of HIV-positive individuals. Furthermore, we analysed the dose-dependent effect of the above mentioned cytokines on KS-derived cells in vitro. The KS-derived cell culture medium demonstrated significantly higher concentrations than the fibroblast cell lines in view of the following cytokines: sIL-2R, IL-1beta, IL-6, TNF-alpha, GM-CSF, IFN-gamma (p<0.05). The most pronounced differences between KS-cells and fibroblasts were observed for IL-1beta and IFN-gamma. The antiproliferative effect of IFN-beta and IFN-gamma began at a concentration of 20 and 50 IU/ml, respectively, whereas for IFN-alpha an antiproliferative effect was observed at a concentration of 100 U/ml. Furthermore we observed a proliferative effect in low concentrations (2-5 IU/ml) of IFN-gamma in our in vitro model
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PMID:Cytokine profile of HIV-positive Kaposi's sarcoma derived cells in vitro. 1008 75