S1P1 downregulation tailors CD8+ T-cell residence time in lymph nodes to the strength of the antigenic stimulation

Abstract

T cells are sequestered for several days in lymph nodes following antigen recognition but the precise mechanism regulating their timing of egress is not fully understood. In particular, whether interactions with antigen-presenting cells (APCs) and/or strength of the TCR stimulation shape T-cell residence time is unclear. We report here that the probability of T-cell egress decreases upon stimulation with high affinity TCR ligands. In contrast, low affinity peptides favor early egress, a phenomenon that could be reversed by sustaining antigen availability. The delayed egress of high affinity T cells could not be accounted by physical sequestration by APCs. Instead, we found that the sphingosine-1-phosphate receptor (S1P1) downregulation mirrors the strength and persistence of the TCR stimulation, limiting egress of high affinity T cells. We propose that S1P1 acts as a rheostat to tailor T-cell residence time in the lymph node to the local availability of antigen and to optimize the expansion of high affinity T cells.