IL-12 induces human T cells secreting IL-10 with IFN-gamma.
A clear differentiation of Th1 and Th2 cytokine-secreting subsets in humans has not yet been defined. To further examine cytokine-directed differentiation of human T cell responses to both exogenous and autoantigens, we generated 346 short term T cell lines at limiting dilutions from six normal individuals to tetanus toxoid and myelin basic protein in the presence of IL-2 with or without the addition of IL-12 and anti-IL-4 mAb. T cell lines were examined for [3H]thymidine incorporation and cytokine secretion of IFN-gamma, IL-4, and IL-10. After culture in the presence of IL-12 and anti-IL-4 mAb, the predominant T cell response to Ag stimulation was simultaneous secretion of IL-10 and IFN-gamma. The concomitant secretion of IL-10 and IFN-gamma by T cells was confirmed by stimulating lines in the absence of APCs with plate-bound anti-CD3 mAb after two rounds of Ag-specific stimulation. Moreover, IL-12 enhanced IL-10 and IFN-gamma production in a myelin basic protein-reactive T cell clone, demonstrating that a differentiated T cell clone could be induced to secrete both cytokines. The addition of a neutralizing anti-IFN-gamma Ab to cultures with IL-12 and anti-IL-4 mAb during the generation of tetanus toxoid-reactive lines had no effect on the induction of IL-10 and IFN-gamma secretion, indicating that IL-12 and not IFN-gamma was responsible for the induction of this subset of T cells. Thus, in human T cells, IL-12 induces concomitant secretion of IL-10 and IFN-gamma.
Windhagen
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A
Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Anderson
D E
DE
Carrizosa
A
A
Williams
R E
RE
Hafler
D A
DA
D000328:Adult; D000911:Antibodies, Monoclonal; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism*; D018664:Interleukin-12 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000378:metabolism; D008875:Middle Aged; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism*; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma