FOXO1 opposition of CD8 + T cell effector programming confers early memory properties and phenotypic diversity

著者: Arnaud Delpoux, Chen-Yen Lai, Stephen Μ. Hedrick, Andrew L. Doedens - Proceedings of the National Academy of Sciences, PNAS 2017 被引用: 94

Significance Acute infection with intracellular pathogen results in the expansion and effector differentiation of pathogen-specific CD8 + T cells, most of which die after pathogen clearance. The factors and steps controlling CD8 + T cell differentiation in response to acute infection are not fully understood. We find FOXO1 and TCF7 drive postinfection immune memory characteristics in cells expressing low TIM3, where TCF7 actively down-regulates the cytotoxic molecule GZMB and reduces terminally differentiated KLRG1 high effector abundance. We further report the creation of a continuum of CD8 + T cell phenotypes, ranging from terminal effector cells to long-lived immune-memory cells, dependent on FOXO1 and TCF7. We conclude FOXO1 and TCF7 are essential to oppose cytotoxic/terminal differentiation programs and enable full phenotypic diversity of postinfection CD8 + T cells.