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Early signaling events that underlie fate decisions of naive CD 4 + T cells toward distinct T‐helper cell subsets
Author(s) -
Yamane Hidehiro,
Paul William E.
Publication year - 2013
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12032
Subject(s) - biology , t cell , t cell receptor , microbiology and biotechnology , immune system , antigen presenting cell , immunology , cytokine , cellular differentiation , population , cell fate determination , antigen , natural killer t cell , transcription factor , genetics , gene , medicine , environmental health
Summary CD 4 + T‐helper (Th) cells are a major cell population that play an important role in governing acquired immune responses to a variety of foreign antigens as well as inducing some types of autoimmune diseases. There are at least four distinct Th cell subsets (Th1, Th2, Th17, and inducible T‐regulatory cells), each of which has specialized functions to control immune responses. Each of these cell types emerge from naive CD 4 + T cells after encounter with foreign antigens presented by dendritic cells ( DC s). Each Th cell subset expresses a unique set of transcription factors and produces hallmark cytokines. Both T‐cell receptor ( TCR )‐mediated stimulation and the cytokine environment created by activated CD 4 + T cells themselves, by ‘partner’ DC s, and/or other cell types during the course of differentiation, play an important role in the fate decisions toward distinct Th subsets. Here, we review how TCR ‐mediated signals in collaboration with the cytokine environment influence the fate decisions of naive CD 4 + T cells toward distinct Th subsets at the early stages of activation. We also discuss the roles of TCR ‐proximal signaling intermediates and of the Notch pathway in regulating the differentiation to distinct Th phenotypes.