Signal integration by CD8 T cells during activation

Jens Stein

Naive CD8 T cell activation by pMHC-presenting dendritic cells (DCs) has evolved over millions of years within secondary lymphoid organs (SLOs) to expedite effector CD8 T cell generation against rapidly propagating microbes. Yet, how the SLO stroma affects T cell - DC interactions and subsequent effector T cell differentiation is incompletely understood. Here, we report that lymphoid stroma-secreted factors act as a rheostat of interaction duration by gradually inducing T cell detachment from DCs. Defects in the stromal rheostat led to sustained T cell priming, yielding effector T cells with high expression of inhibitory receptors and impaired antimicrobial activity. In sum, our results uncover a lymphoid tissue checkpoint restricting T cell - DC interaction duration in order to accelerate cytotoxic effector T cell generation and to prevent dysfunctional T cell differentiation.