Research ArticleT CELL DIFFERENTIATION

TCR signal strength controls the differentiation of CD4+ effector and memory T cells

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Science Immunology  20 Jul 2018:
Vol. 3, Issue 25, eaas9103
DOI: 10.1126/sciimmunol.aas9103

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Signal strength seals fate

T cell differentiation into effector and memory T cell subsets is influenced by T cell receptor (TCR) signals. Snook et al. examine how TCR signals influence CD4+ T cell differentiation using a panel of cloned TCRs that recognize the same MHC II–restricted epitope of lymphocytic choriomeningitis virus. Strong TCR signals were associated with TH1 differentiation, whereas lower TCR signal strength corresponded with follicular helper T cell and memory T cell differentiation. Low CD25 expression by early effector T cells also predicted memory differentiation, although CD25 expression levels were not predictive of recall responses. Enhanced TCR signaling via knockdown of SHP-1 favored TH1 over Tfh and memory T cell differentiation. These results indicated that stronger TCR signaling promotes terminal effector TH1 differentiation.