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The Journal of Immunology, Vol 155, Issue 1 111-117, Copyright © 1995 by American Association of Immunologists
ARTICLES |
JD Marshall, H Secrist, RH DeKruyff, SF Wolf and DT Umetsu
Department of Pediatrics, Stanford University, CA 94305, USA.
IL-12 influences cytokine synthesis in unprimed CD4+ T cells by enhancing IFN-gamma synthesis and enhancing the development of Th1 cells, but its effects upon Ag-primed T cells, which are thought to have relatively fixed cytokine profiles, is less clear. We investigated the capacity of IL-12 to modify cytokine synthesis in allergen-specific human CD4+ T lymphocytes from allergic donors after in vitro stimulation. CD4+ T cells were obtained from the peripheral blood of subjects with allergic rhinitis, depleted of activated T cells, and cultured with APCs and allergen. IL-12 dramatically inhibited the development of IL-4 and IL-10 synthesis, while it enhanced T cell secretion of IFN-gamma and IL-2, and enhanced Ag-specific T cell proliferation. The inhibitory effect of IL-12 on IL-4 synthesis was not dependent on the presence of IFN-gamma, was greatest when IL-12 was added at the initiation of culture, and was minimal when added late, indicating that resting memory CD4+ T cells were more sensitive than activated CD4+ T cells to the effects of IL-12. The effect of IL-12 on IL-4 and IL-10 synthesis was not dependent on the APC type, because IL- 12 decreased IL-4 synthesis when either B cells or monocytes served as APCs. These results indicate that IL-12 may be therapeutically beneficial in the treatment of allergic diseases in which allergen- specific T cells characteristically produce enhanced quantities of IL-4 and IL-10.
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