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A two-step model of T cell subset commitment: antigen-independent commitment of T cells before encountering nominal
Makoto Kanoh1, Teruyoshi Uetani, Hirokazu Sakan
1Department of Immunology and Host Defenses, Ehime University School of Medicine, Shigenobu, Onsen-gun, Ehime 791-0295, Japan.
Abstract:
Pathogenic infections lead to activation of innate immunity followed by induction of a type 1 T cell subset and, therefore, provide a good model to evaluate when T cells commit to type 1 T cells. Here we show a two-step mechanism of T cell subset commitment during pathogenic infection. The first step is mediated by the basal function of macrophage/dendritic cells and is antigen independent. This step modulates the committed precursor frequency of T cell subsets and influences the expression of T-box expressed in T cells (T-bet) and GATA-3 genes. IL-12 and NK cells are not required for this step. The second step requires antigenic stimulation of T cells together with IL-12 or IL-4, and influences on the expression of T-bet and GATA-3. We propose a two-step T cell subset commitment pathway based on these observations. Therefore, pathogenic infections influence functional T cell commitment before T cells encounter nominal antigen.