During the immune response to infection, CD8+ T cells can be directed to develop into effector T cells or memory T cells by various stimuli. Two studies now identify inflammatory chemokine receptors and uncover mechanisms that can direct these fate decisions, which may have clinical implications for promoting memory T cell development in vaccine strategies.

Makoto Kurachi et al. (J. Exp. Med. 208, 1605–1620) reveal the importance of Cxcr3 in T cell fate decisions in mice. After infection, antigen-specific Cxcr3−/− CD8+ T cells failed to contract, leading to a huge expansion of the memory cell component. The Cxcr3−/− CD8+ T cells did not cluster in the marginal zone of the spleen early after infection, so they failed to receive the inflammatory stimuli present in this region that allow them to become effector T cells. The authors therefore suggest that the proximity of the T cells to inflammatory cytokines is important for determining their fate.

In a second paper, Jacob E. Kohlmeier et al. (J. Exp. Med. 208, 1621–1634) confirm that Cxcr3 regulates memory T cell development and also show that Ccr5 is involved. These two receptors help traffic T cells to infected sites, and, consistent with this, the authors found that Cxcr3−/− Ccr5−/− CD8+ T cells differentially localized within the lung compared with wild-type cells. This altered localization hindered the ability of the T cells to reencounter antigen in the lung, thus directing them along the memory pathway, with addition of exogenous antigen allowing T cell activation and effector development. This study highlights antigen exposure at peripheral sites as another mechanism for regulating T cell fate.