In vitro production of antigen-specific T cells from unprimed mice: role of dexamethasone and anti-IL-10 antibodies.
We describe here a culture system for studying the development, in vitro, of antigen-specific CD4 T cells from unprimed mice. T cells from young mice are initially exposed to antigen, such as pigeon cytochrome C or keyhole limpet hemocyanin, in the presence of adherent accessory cells and then allowed to proliferate in the absence of antigen but in the presence of IL-2, 10(-8) M dexamethasone, and antibodies to IL-10. Proliferation and IL-2 production by T cells harvested from such expansion cultures are antigen-dependent but not antigen-specific and at different doses can be either stimulated or inhibited both by the priming antigen and by irrelevant proteins. Antigen-specific T cell reactions can be elicited by any of three modifications of the culture protocol: (a) absorption of nonspecific cells on accessory cell monolayers bearing irrelevant proteins; (b) increased doses of dexamethasone during the expansion phase; or (c) a second cycle of antigen activation and antigen-free expansion. These observations provide a foundation for further analysis of in vitro maturation of primary immune responses and suggest an important role for IL-10 and glucocorticoids in regulating the early stages of activation and proliferation by naive T cells.
Dozmorov
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Department of Pathology, University of Michigan School of Medicine, Ann Arbor, USA.
Miller
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RA
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003574:Cytochrome c Group / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology*; D004306:Dose-Response Relationship, Immunologic; D005938:Glucocorticoids / Q000494:pharmacology*; D007156:Immunologic Memory; D007158:Immunologic Techniques; D016753:Interleukin-10 / Q000502:physiology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL
D000941:Antigens; D003574:Cytochrome c Group; D005938:Glucocorticoids; D007376:Interleukin-2; D016753:Interleukin-10; D003907:Dexamethasone