Autor: |
Bejarano, Maria-Teresa, Malefyt, René de Waal, Abrams, John S., Bigler, Mike, Bacchetta, Rosa, de Vries, Jan E., Roncarolo, Maria-Grazla |
Zdroj: |
International Immunology; Dec1992, Vol. 4 Issue 12, p1389-1397, 9p |
Abstrakt: |
The effects of IL-10 on the generation of alloreactlvity in primary mixed lymphocyte cultures (MLCs) were investigated. IL-10 inhibited in a dose-dependent fashion the alloantlgen-induced prollferatlve responses. The suppressive effect was maximal when IL-10 was added at the beginning of the cultures, suggesting that it acts on the early stages of T cell activation. The proliferatlve responses were enhanced in the presence of a neutralizing anti-IL-10 mAb, indicating that endogenously produced IL-10 suppresses proliferation in primary MLC. The inhibitory effects of IL-10 were observed irrespective of whether irradiated allogenelc peripheral blood mononuclear cells, purified monocytes or freshly isolated B cells were used as stimulator cells. The proliferation of both the CD4 and CD8 T cell subsets was inhibited to a similar extent. The reduced proliferatlve responses were only minimally restored by high concentrations of exogenous IL-2, indicating that the effects of IL-10 are not exclusively due to inhibition of IL-2 synthesis. Furthermore, the production of IL-2, interferon (IFN)-γ, IL-6, granulocyte macrophage colony stimulating factor, and tumor necrosis factor-α in primary MLCs was diminished by IL-10 and enhanced in the presence of antl-IL-10 mAb. The strongest effects were observed on the production of IFN-γ. Although IL-10 reduces the proliferative responses, the ratios of CD3CD4 and CD3CD8 T cells remained the same in IL-10 treated and control cultures, yet the percentages of activated CD3 T cells, as judged by CD25 and HLA-DR expression, were consistently reduced. The generation of allospecific cytotoxlclty was also inhibited by IL-10 and enhanced in the presence of antl-IL-10 mAb. These data indicate that IL-10 has important regulatory effects on allogeneic responses . [ABSTRACT FROM PUBLISHER] |
Databáze: |
Complementary Index |
Externí odkaz: |
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