T helper type 1 development of naive CD4+ T cells requires the coordinate action of interleukin-12 and interferon-γ and is inhibited by transforming growth factor-β

摘要: It was observed in vitro and vivo that both interferon (IFN)-gamma interleukin (IL)-12 can promote the development of T helper type 1 (TH1) cells. Since IL-12 shown to be a costimulator for production IFN-gamma by or natural killer (NK) cells, might play only an indirect role TH1 differentiation providing which represents essential factor. Using anti-CD3 monoclonal antibody (mAb) activation naive CD4+ cells absence accessory we could demonstrate costimulation alone results marginal development. Similarly, is poor inducing towards phenotype. Our data indicate cytokines are required allow optimal has dual role, it promotes direct also enhances serves as second autocrine mechanism. Another cytokine reported favor certain experimental systems transforming growth factor (TGF)-beta. With employed this study TGF-beta strongly inhibited triggered well IL-12-induced When combined with anti-IFN-gamma mAb neutralization endogenous TH1-inducing capacity completely suppressed.