Inhibitory and stimulatory effects of IL-10 on human CD8+ T cells.
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.
Groux
H
H
Immunobiology Department, DNAX Research Institute of Molecular Immunology and Cellular Biology, Palo Alto, CA 94304, USA. groux@dnax.org
Bigler
M
M
de Vries
J E
JE
Roncarolo
M G
MG
D015703:Antigens, CD / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D017635:Clonal Anergy / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D015536:Down-Regulation / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D006131:Growth Inhibitors / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology*; D006680:HLA Antigens / Q000096:biosynthesis; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009000:Monocytes / Q000276:immunology / Q000378:metabolism
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D000939:Epitopes; D006131:Growth Inhibitors; D006133:Growth Substances; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D007519:Isoantigens; D008562:Membrane Glycoproteins; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10