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Immunobiology. 1995 Feb;192(3-4):155-71.

Promotion of macrophage-stimulated autoreactive T cell proliferation by interleukin-10: counteraction of macrophage suppressor activity during tumor growth.

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Department of Biology, Virginia Polytechnic Institute and State University, Blacksburg, USA.


CD4+ autoreactive T cells are a major cell population in regulating immune responses to altered autologous neoplastic cells. Normal autoreactive T cells recognize major histocompatibility complex (MHC) class II molecules in association with self-peptides on antigen-presenting cells, such as macrophages (M phi). Tumor-bearing hosts (TBH) have decreased autoreactivity partly because tumors increase M phi secretion of suppressor molecules like prostaglandin E2 (PGE2) and decrease M phi MHC class II expression. Because interleukin (IL)-10, a cytokine produced by T cells, M phi, and tumor cells, inhibits production of most M phi suppressor molecules, we determined if IL-10 could reverse tumor-induced murine splenic M phi-mediated suppression of autoreactive T cell proliferation. Tumor growth enhanced activated M phi production of PGE2, nitric oxide, and tumor necrosis factor-alpha (TNF-alpha). IL-10 strongly reduced or inhibited M phi production of these molecules. When added to pure normal host (NH) CD4+ T cells, NH syngeneic splenic M phi stimulated autoreactive T cell proliferation more than did TBH splenic M phi. Exogenous IL-10 or M phi preincubation with IL-10 restored TBH M phi-stimulated autoreactivity to normal levels. IL-10 treatment had little or no effect on NH M phi-stimulated autoreactivity. IL-10 inhibited TBH M phi secretion of suppressor molecules in T cell proliferation assays because supernatants from IL-10-pretreated TBH M phi-syngeneic NH T cell cultures had decreased levels of suppressor molecules. When endogenous IL-10 activity was neutralized with anti-IL-10 monoclonal antibody, autoreactive T cell proliferation stimulated by NH or TBH M phi was slightly, but significantly decreased. Although IL-10 is known to inhibit M phi foreign antigen-presenting cell-dependent T cell proliferation, this study shows that IL-10 restores autoreactive T cell functions during tumor growth by counteracting M phi production of inhibitory molecules. These data suggest that IL-10 up-regulates anti-cancer autoreactive T cell responses by down-regulating suppressor M phi activity.

[Indexed for MEDLINE]

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