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)

Two features of simian immunodeficiency virus (SIV) infection are emphasized: a transitory decrease in CD4 T cells in the first 2 weeks of infection followed by CD8 T-cell rise, and immune cell activation occurring by 4 weeks and persisting throughout the illness. The short-term changes included a fall in CD4 T cells by 2 weeks with partial recovery by 4 weeks and a CD8 rise that starts at 2 weeks. Subsequent characterization of CD4 T cells showed reduced expression of HLA-DR and CD25 (IL-2 receptor alpha chain) antigens later in SIV infection. Immune cell activation is evident in increased serum levels of neopterin and soluble CD8 antigen. Serum beta 2-microglobulin changes are less marked. Activation of CD8 T cells is reflected by increased percentages of cells expressing HLA-DR antigen. The B-cell numbers increased late in the course of SIV infection. Increased expression of the CD78 (Leu 21) activation phenotype was also seen in some monkeys. The immune activation changes (serum neopterin levels) induced by SIV infection in rhesus macaques appear to be associated with duration of illness, although the number of monkeys observed until death were too few for conclusive data. Thus, immune activation as well as T-cell deficiency may reflect significant immunopathogenic processes in SIV-induced disease.
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PMID:Acute lymphoid changes and ongoing immune activation in SIV infection. 154 74

Northern blot analysis and a highly sensitive methodology for mRNA phenotyping, polymerase chain reaction (PCR), were used to explore the basis for the synergism between CD3/alpha beta T cell receptor (TCR) and the CD2 antigen-derived signals in promoting proliferation of T cells. Northern blotting of RNA isolated from highly purified normal human T cells revealed that crosslinking of anti-TCR-1 (a mAb directed at a framework determinant of the TCR) and OKT11 (a mAb directed at the SRBC-binding epitope of the CD2 antigen) induced the expression of the interleukin-2 gene and the gene for IL-2 receptor alpha, mRNA phenotyping by PCR revealed that crosslinkage of TCR with the CD2 antigen, and not independent crosslinking of TCR or the CD2 antigen, results in the induction of IL-2, IL-2 receptors alpha and beta, and IL-4-specific transcripts. Highly purified CD4+ T cells, as well as CD8+ T cells proliferated by crosslinking TCR with CD2 antigen. Moreover, crosslinkage of TCR with the CD2 antigen and not of either antigen with the CD4 antigen (on the surface of CD4+ T cells) or the CD8 antigen (on the surface of CD8+ T cells) resulted in marked proliferation. Our demonstration that the CD2 antigen-derived signal(s) contribute to the expression of growth promoting genes elicited via the TCR, and that the CD2 antigen is more efficient compared with the CD4 or CD8 antigen in evoking T cell proliferation, suggests that autoimmunity as well as alloimmunity might be regulated by targeting the CD2 antigen.
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PMID:The molecular basis for the synergism between the CD3/alpha beta T cell receptor and the CD2 antigen-derived signals in promoting T-cell proliferation. 167 15

After a 5-day period of continuous intravenous infusion of recombinant interleukin 2 (rIL-2) in seven patients with malignant melanoma or gastric or pancreatic cancer, different lymphocyte subsets were separated from patients' blood and tested ex vivo for cytotoxic activity against various tumour cell lines. Lytic activity was mediated by CD3+CD56+, CD3-CD56+, CD3-CD2+ and CD8+CD56+ lymphocytes. No cytotoxic activity could be observed within the CD3+CD56-, CD3+CD2+ or CD4+ T cell subsets. To characterize CD56+ cytotoxic cells further, the expression of other antigens on this population was analysed before and after IL-2 therapy. CD3, CD4, CD16 and CD57 antigens were weakly expressed, and the IL-2 receptor (CD25) was not detectable on these cells either before and after treatment with IL-2. In contrast, increased expression of CD2. CD8 and HLA-DR antigens occurred following therapy. The divergence of CD3 and CD8 antigen expression after IL-2 therapy was caused by an increase in CD3-CD8+ cells, detectable as a low-density CD8+ subset. This study shows that cytotoxic activity of in vivo IL-2-activated killer cells is predominantly, but not exclusively, mediated by CD3-CD56+ lymphocytes, partially coexpressing the CD8 antigen and lacking the expression of CD16 antigens.
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PMID:Cytotoxic activity and phenotypic characteristics of lymphocyte subsets after therapy of cancer patients with interleukin-2. 187 92

Transmembrane signaling of normal human T cells was explored with mAbs directed at TCR, CD2, CD4, CD5, or CD8 antigens and highly purified CD4+ T cells and CD8+ T cells. Our experiments explicitly show that: (a) crosslinkage of TCR with the CD2 antigen, and not independent crosslinking of TCR and of CD2 antigen or crosslinking of either protein with the CD4 or CD8 antigen induces significant proliferation independent of co-stimulatory signals (e.g., accessory cells, recombinant lymphokines, or tumor promoter), (b) F(ab')2 fragments of mAb directed at the TCR and F(ab')2 anti-CD2, crosslinked with F(ab')2 fragments of rabbit anti-mouse IgG, promote the proliferation of highly purified T cells, (c) a prompt and sustained increase in intracellular free Ca2+ concentration results from crosslinkage of TCR with the CD2 antigen, (d) T cell proliferation induced by this novel approach is curtailed by EGTA and by direct or competitive inhibitors of PKC, (e) crosslinkage of TCR with the CD2 antigen results in the transcriptional activation and translation of the gene for IL-2 and in the expression of IL-2 receptor alpha (CD25), (f) anti-CD25 mAbs inhibit T cell proliferation initiated by crosslinkage of TCR with the CD2 antigen, and recombinant IL-2 restores the proliferative response. Our first demonstration that crosslinkage of TCR with the CD2 antigen induces proliferation of normal human CD4+ T cells and CD8+ T cells, in addition to revealing a novel activation mechanism utilizable by the two major subsets of T cells, suggest that the CD2 antigen might be targeted for the regulation of antigen-specific T cell immunity (e.g., organ transplantation).
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PMID:A novel model for antigen-dependent activation of normal human T cells. Transmembrane signaling by crosslinkage of the CD3/T cell receptor-alpha/beta complex with the cluster determinant 2 antigen. 197 76

Sequential samples of serum and cerebrospinal fluid (CSF), from 9 patients with herpes simplex encephalitis (HSE), were analyzed for cytokines and soluble cytokine receptors. The response to herpes simplex virus was characterized by a vigorous compartmentalized immune response. The intrathecal response comprised three different phases: an acute stage (first week of illness), characterized by elevated CSF levels of interleukin (IL)-6 and interferon-gamma; an early convalescence stage (weeks 2-6 after onset of disease), associated with peaking levels of tumor necrosis factor-alpha and late markers of the specific T cell-mediated immune response, soluble IL-2 receptor, and soluble CD8 antigen (sCD8); and finally, a late convalescence stage, lasting months to years and associated with persistently increased levels of sCD8 in particular. These findings show the compartmentalization and kinetics of the inflammatory response in HSE and demonstrate persistence of the intrathecal inflammatory process, which may have implications for antiviral and antiinflammatory therapy.
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PMID:Cytokines and other markers of intrathecal immune response in patients with herpes simplex encephalitis. 807 27

Serum cytokine profiles, T-cell subsets, and general parameters of immune activation were evaluated in 15 patients with acute primary HIV-1 infection, and compared with those obtained from 18 patients with acute primary Epstein-Barr virus (EBV) infection and from 18 control subjects in order to elucidate possible defects of immune response to HIV in early phases of virus-host interaction. Mean CD4+ cell count, serum concentrations of interleukin (IL)-2, IL-4, soluble IL-2 receptor (sIL-2R), tumor necrosis factor (TNF)-alpha, 5'-neopterin, and beta 2-microglobulin were significantly lower in acute HIV-1 infection than in EBV infection. Both acute HIV-1 and EBV infections were characterized by significantly higher mean CD8+ cell count and soluble CD8 antigen (sCD8) levels compared to control subjects, while acute HIV-1 infection was accompanied by the highest interferon (IFN)-gamma serum concentrations. In primary HIV-1 infection, significant impairment of CD4+- mediated T-helper function may lead to viral escape and persistence of infection despite an early and vigorous CD8+ T-lymphocyte activation.
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PMID:Serum cytokine profiles in acute primary HIV-1 infection and in infectious mononucleosis. 859 86

We performed a placebo-controlled study to evaluate the effects of immunomodulatory treatment with thalidomide on HIV levels, TNF-alpha levels, and immune status of 31 HIV-infected individuals, after temporary suppression of viral replication with antiretroviral drugs. Treatment with a combination of zidovudine and lamivudine (ZDV/LMV) for 14 days resulted in a median decline in plasma viremia of 1.94 log10 RNA equivalents/ml. After discontinuation of ZDV/LMV, thalidomide therapy (200 mg/day for 4 weeks) did not retard the prompt return of HIV titers to the pretreatment levels, and had no effect on plasma levels of TNF-alpha. In contrast, thalidomide treatment resulted in significant immune stimulation. We observed increased levels of plasma soluble IL-2 receptor, soluble CD8 antigen, and IL-12 (p < 0.01 for all parameters), as well as increased cutaneous delayed-type hypersensitivity reactions to recall antigens (p < 0.01) in thalidomide-treated patients. These changes were associated with a median increase in HIV titer of 0.2 log10 RNA equivalents/ml in the thalidomide-treated group (p < 0.05), which resolved after stopping the drug. Further studies were performed in vitro to elucidate the mechanism of thalidomide-induced immune stimulation. When purified T cells from HIV-infected individuals were stimulated by immobilized anti-CD3 in the presence of thalidomide, a costimulatory effect of the drug was observed, resulting in increased production of IL-2 and IFN-gamma, and increased T cell-proliferative responses. Further experiments showed that thalidomide increased IL-12 production by antigen-presenting cells in a T cell-dependent manner. Our findings suggest a potential application for thalidomide as a novel immune adjuvant in HIV disease.
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PMID:Thalidomide stimulates T cell responses and interleukin 12 production in HIV-infected patients. 1048 Jun 30