CXCR3 expression affects the balance of effector and memory CD8 T cell generation (46.6)

Abstract

Abstract In response to infection, activated CD8 T cells differentiate in vivo into a heterogeneous population of cells consisting of short-lived, terminally differentiated effector cells and memory precursor cells that give rise to long-lived memory cells. The strength and duration of antigenic stimulation and inflammatory signals influence CD8 T cell differentiation and the balance between these two fates. However, cell extrinsic cues, such as chemokines, that affect the localization and hence the exposure of CD8 T cells to antigenic and inflammatory signals are not completely understood. Here, we find that the inflammatory chemokine receptor CXCR3 is upregulated on activated CD8 T cells and influences their differentiation. CXCR3 guides activated CD8 T cells towards marginal zone areas where they are exposed to antigenic and potentially inflammatory stimuli. In the absence of CXCR3 expression, activated CD8 T cells are localized to the T zones of the splenic white pulp where they are less likely to receive antigenic stimulation. The increased exposure to antigen is associated with an increase in the generation of short-lived effector cells while the decreased exposure to antigen is associated with a quantitative and qualitative enhancement of memory cells. Our findings demonstrate that chemokine receptors and T cell positioning in secondary lymphoid organs can influence the balance of effector and memory T cell generation.