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

Interleukin-10 (IL-10) has various immunomodulatory actions depending on the target cell type. Some of these effects have been shown to be owing to its ability to down-regulate surface expression of markers, for example HLA-DR on macrophages and CD25 (IL-2 receptor alpha chain) on B cells. In this report we show that preincubation of IL-10 for 24 hr up-regulates expression of the activation marker CD25, but not HLA-DR on cloned T cells of various phenotypes such as CD4+, CD8+, CD4- CD8- alpha beta and gamma delta T-cell receptor (TCR)-expressing cells. This up-regulation of CD25 was accompanied by an increase in the T cells IL-2-dependent proliferative response in 63% of the CD4+ clones and 100% of the CD8+, CD4-, CD8- alpha beta and gamma delta TCR+ clones analysed. IL-10 was also shown to be at least partly responsible for the up-regulation of CD25 on mitogen-activated peripheral blood mononuclear cells, suggesting that IL-10 has this CD25 modulatory effect within a more physiological environment. Our data suggest that IL-10 can have a multitude of effects on human T cells, and should not be considered exclusively as an immunoinhibitory cytokine.
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PMID:IL-10 enhances expression of the IL-2 receptor alpha chain on T cells. 783 55

Interleukin-10 (IL-10) is a multifunctional cytokine that can exert suppressive and stimulatory effects on T cells. It was investigated whether IL-10 could serve as an immunostimulant for specific CD8(+) cytotoxic T cell (CTL) in vivo after vaccination and, if so, under what conditions. In tumor prevention models, administration of IL-10 before, or soon after, peptide-pulsed primary dendritic cell immunization resulted in immune suppression and enhanced tumor progression. Injection of IL-10, however, just after a booster vaccine significantly enhanced antitumor immunity and vaccine efficacy. Analysis of spleen cells derived from these latter animals 3 weeks after IL-10 treatment revealed that the number of CD8(+) CD44(hi) CD122(+) T cells had increased and that antigen-specific proliferation in vitro was enhanced. Although cytotoxicity assays did not support differences between the various treatment groups, 2 more sensitive assays measuring antigen-specific interferon-gamma production at the single-cell level demonstrated increases in the number of antigen-specific responder T cells in animals in the vaccine/IL-10 treatment group. Thus, IL-10 may maintain the number of antitumor CD8(+) T cells. In adoptive transfer studies, the ability of IL-10 to maintain CTL function could be enhanced by the depletion of CD4(+) T cells. This suggests that IL-10 mediates contrasting effects on both CD4(+) and CD8(+) T cells that result in either immune dampening or immune potentiation in situ, respectively. Appreciation of this dichotomy in IL-10 immunobiology may allow for the design of more effective cancer vaccines designed to activate and maintain specific CD8(+) T-cell effector function in situ.
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PMID:Interleukin-10 promotes the maintenance of antitumor CD8(+) T-cell effector function in situ. 1156 1