Abstract
T cells rapidly undergo contraction upon viral clearance, but how Tcell function and fate are determined during this phase is unclear. During the contraction phase of an acute infection with lymphocytic choriomeningitis virus, we found that virus-specific CD8+ Tcells within the splenic red pulp (RP) had higher two-dimensional (2D) effective affinity than those within the white pulp (WP). This increased antigen recognition of RP-derived CD8+ Tcells correlated with more efficient target cell killing and improved control of viremia. FoxP3+ regulatory Tcells and cytokine TGF-β limited the 2D-affinity in the WP during the contraction phase. Anatomical location drove gene expression patterns in CD8+ Tcells that led to preferential differentiation of memory precursor WP Tcells into long-term memory cells. These results highlight that intricate regulation of Tcell function and fate is determined by anatomic compartmentalization during the early immune contraction phase.
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