Synergistic inhibitory activities of interleukin-10 and dexamethasone on human CD4+ T cells1
| Autor: | Nicola Mascetra, Francesca B. Aiello, Mauro Brunetti, Piero Musiani, Franco O. Ranelletti, Nicola Martelli |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Interleukin 2
Transplantation medicine.medical_specialty biology CD3 Interleukin Tyrosine phosphorylation Pharmacology chemistry.chemical_compound Interleukin 10 Endocrinology chemistry Interleukin 15 Internal medicine polycyclic compounds medicine biology.protein Cytotoxic T cell Receptor hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Transplantation. 74:1152-1158 |
| ISSN: | 0041-1337 |
| Popis: | BACKGROUND: We have previously demonstrated that interleukin (IL)-10 synergizes with dexamethasone (Dex) in inhibiting proliferation of human T cells, stimulated in an antigen-presenting cell (APC)-dependent manner. Because IL-10 effectively inhibits APC accessory functions, the synergism could have been a result of its effect on APC. We then investigated the effects of Dex and IL-10 on T-cell subpopulations, stimulated in an APC-independent manner. METHODS: CD4 and CD8 T cells were stimulated with anti-CD3, with or without Dex and IL-10, alone or in combination. Proliferation, glucocorticoid (GC) receptor binding, anti-CD3-induced tyrosine phosphorylation, IL-2 production, and expression of IL-2 receptor alpha, beta, and gamma chains were evaluated. The pharmacologic interactions were analyzed using the isobole method. RESULTS: IL-10 synergized with Dex in inhibiting CD4 but not CD8 T-cell proliferation. The synergism was not associated with modifications of GC receptor number or affinity, nor with modifications of anti-CD3-induced tyrosine phosphorylation. IL-10 synergized with Dex in inhibiting IL-2 production and increased Dex inhibitory effect on the expression of the IL-2 receptor alpha chain, which is up-regulated by CD3 stimulation and IL-2. Only Dex inhibited the beta and gamma chain expression, which, interestingly, is not up-regulated by IL-2. IL-2, as well as IL-7 and IL-15, reversed the effects of IL-10 but not those of Dex. CONCLUSIONS: IL-10 synergizes with Dex in inhibiting CD4 T-cell proliferation. Its synergizing effect is mediated by the inhibition of IL-2 production. Dex exerts additional activities, such as the inhibition of beta and gamma chain expression. Therefore, IL-10 could be useful for the enhancement of GC-based immunosuppressive therapies. |
| Databáze: | OpenAIRE |
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