Differential effects of interleukin-10 on the expression of HLA class II and CD1 molecules induced by granulocyte/macrophage colony-stimulating factor/interleukin-4.
Interleukin (IL)-10 down-regulates HLA class II molecules, whether constitutively expressed or up-regulated by interferon-gamma or IL-4 on monocytes but not on B lymphocytes. In this study we show that IL-10 does not inhibit HLA class II expression induced by the combination granulocyte/macrophage colony-stimulating factor and IL-4 on monocytes, although it simultaneously abrogates the expression of CD1 molecules induced by the same combination of cytokines. CD1 molecules can act as element of genetic restriction for CD4- CD8- T lymphocytes, and the suppression of CD1 expression by IL-10 abolished antigen presentation to CD1-restricted CD4- CD8- T cell receptor-positive T cells. Although HLA class II expression was not down-regulated by IL-10, the antigen specific proliferative response of CD4+ T cells was nevertheless decreased. This was not caused by down-regulation of known co-stimulatory molecules such as B7.1, B7.2 and ICAM-1. IL-10 decreased the antigen specific proliferative response further by directly influencing the T lymphocytes. Our results indicate that IL-10 exerts some of its immunoregulatory functions by differential modulation of antigen presenting molecules, induced by the same combination of cytokines.
Thomssen
H
H
Kennedy Institute of Rheumatology, Sunley Division, Hammersmith, London, GB.
Kahan
M
M
Londei
M
M
D017951:Antigen Presentation; D018949:Antigens, CD1 / Q000096:biosynthesis*; D018122:B7-1 Antigen / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D018949:Antigens, CD1; D018122:B7-1 Antigen; D000949:Histocompatibility Antigens Class II; D016753:Interleukin-10; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor