Inhibition of TGF-?1 signaling promotes central memory T cell differentiation.

ABSTRACT: This study affirmed that isolated CD8(+) T cells express mRNA and produce TGF-? following cognate peptide recognition. Blockage of endogenous TGF-? with either a TGF-?-blocking Ab or a small molecule inhibitor of TGF-?RI enhances the generation of CD62L(high)/CD44(high) central memory CD8(+) T cells accompanied with a robust recall response. Interestingly, the augmentation within the central memory T cell pool occurs in lieu of cellular proliferation or activation, but with the expected increase in the ratio of the Eomesoderm/T-bet transcriptional factors. Yet, the signal transduction pathway(s) seems to be noncanonical, independent of SMAD or mammalian target of rapamycin signaling. Enhancement of central memory generation by TGF-? blockade is also confirmed in human PBMCs. The findings underscore the role(s) that autocrine TGF-? plays in T cell homeostasis and, in particular, the balance of effector/memory and central/memory T cells. These results may provide a rationale to targeting TGF-? signaling to enhance Ag-specific CD8(+) T cell memory against a lethal infection or cancer.

SUBMITTER: Takai S 

PROVIDER: S-EPMC3889640 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature