Abstract
IL-10 is a well-documented immunosuppressant that inhibits macrophage-dependent Ag presentation and CD4+ T cell proliferation in vitro. We report that IL-10 inhibits alloantigen-specific proliferative responses and induces a long lasting anergic state in human purified CD8+ T cells when added concomitantly with the Ag in the presence of APC. Moreover, the generation of allospecific cytotoxic activity is inhibited by IL-10. These effects are indirect and are mediated through inhibition of the costimulatory functions of APC. In contrast, IL-10 has no direct inhibitory effects on the proliferation of purified CD8+ T cells activated by anti-CD3 mAb and promotes the growth of activated CD8+ T cells in combination with low doses of IL-2. Taken together, these results indicate that IL-10 has differential effects on CD8+ T cells depending on their state of activation, which may explain both the enhancing and inhibitory effects observed after IL-10 treatment in different in vivo experimental models.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD / biosynthesis
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B7-1 Antigen / biosynthesis
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B7-2 Antigen
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CD8-Positive T-Lymphocytes / drug effects
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CD8-Positive T-Lymphocytes / immunology*
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Clonal Anergy / drug effects
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Cytotoxicity, Immunologic / drug effects
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Down-Regulation / immunology
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Epitopes / immunology
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Growth Inhibitors / pharmacology*
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Growth Substances / pharmacology*
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HLA Antigens / biosynthesis
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Histocompatibility Antigens Class I / biosynthesis
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Humans
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Immunosuppressive Agents / pharmacology*
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Intercellular Adhesion Molecule-1 / biosynthesis
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Interleukin-10 / pharmacology*
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Interleukin-2 / pharmacology
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Isoantigens / immunology
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Lymphocyte Activation / drug effects
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Lymphocyte Culture Test, Mixed
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Membrane Glycoproteins / biosynthesis
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Monocytes / immunology
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Monocytes / metabolism
Substances
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Antigens, CD
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B7-1 Antigen
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B7-2 Antigen
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CD86 protein, human
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Epitopes
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Growth Inhibitors
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Growth Substances
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HLA Antigens
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Histocompatibility Antigens Class I
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Immunosuppressive Agents
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Interleukin-2
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Isoantigens
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Membrane Glycoproteins
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Intercellular Adhesion Molecule-1
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Interleukin-10