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It is unclear where within tissues subsets of effector and memory CD8 T cells persist during viral infection and whether their localization affects function and long-term survival. Following lymphocytic choriomeningitis virus infection, we found most killer cell lectin-like receptor G1 (KLRG1) lo IL-7R hi effector and memory cells, which are long-lived and high proliferative capacity, in the T cell zone of the spleen. In contrast, KLRG1 hi IL-7R lo cells, which appear terminally differentiated and have shorter life spans, were exclusively localized to the red pulp. KLRG1 lo IL-7R hi T cells homed to the T cell zone using pertussis toxin-sensitive chemokine receptors and appeared to contact gp38+ stromal cells, which produce the chemokines CCL19 and CCL21 and the T cell survival cytokine IL-7. The transcription factors T-bet and B lymphocyte-induced maturation protein-1 controlled effector CD8 T cell splenic migration …