Strength of inflammatory stimuli during the early expansion phase plays a crucial role in effector and memory cell fate-decision of CD8+ T cells. But it is not known how early lymphocyte distribution after infection impacts this process. Here we demonstrate that chemokine receptor CXCR3 is involved in CD8 T-cell commitment to effector rather than memory fates by regulating T-cell recruitment to an antigen/inflammation site. After systemic viral (VV-OVA) and bacterial (LM-OVA) infection, contraction of CXCR3KO antigen-specific CD8 T cells is significantly attenuated, resulting in massive accumulation of fully functional memory CD8 T cells. Unlike WT cells, CXCR3KO antigen-specific CD8 T cells fail to cluster early after infection at the marginal zone in the spleen, where inflammatory cytokines such as IL-12 and IFNα are abundant, thus receiving relatively weak inflammatory stimuli. Consequently, CXCR3KO CD8 T cells exhibit shortened expression of CD25, and preferentially differentiate into memory precursor effector cells as opposed to WT CD8 T cells. This series of events has important implications for development of vaccination strategies to generate increased numbers of antigen-specific memory CD8 T cells via inhibition of CXCR3-mediated T-cell migration to inflamed microenvironments.
- Copyright © 2011 by The American Association of Immunologists, Inc.