IL-12 inhibits the production of IL-4 and IL-10 in allergen-specific human CD4+ T lymphocytes.
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.
Marshall
J D
JD
Department of Pediatrics, Stanford University, CA 94305, USA.
Secrist
H
H
DeKruyff
R H
RH
Wolf
S F
SF
Umetsu
D T
DT
D000938:Antigen-Presenting Cells / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D002478:Cells, Cultured; D006801:Humans; D006967:Hypersensitivity / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy
D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma