CD103 fate mapping reveals that intestinal CD103 tissue-resident memory T cells are the primary responders to secondary infection.

Tissue-resident memory T (T) cells remain poised in the tissue and mediate robust protection from secondary infection. T cells within the intestine and other tissues are heterogeneous in their phenotype and function; however, the contributions of these T subsets to secondary infection remain poorly defined. To address the plasticity of intestinal T subsets and their role in local and systemic immunity, we generated mice to fate map intestinal CD103 T cells and track their location and function during secondary infection with . We found that CD103 T cells remained lodged in the tissue and were poorly reactivated during secondary challenge. CD103 T cells were the primary responders to secondary infection and expanded within the tissue, with limited contribution from circulating memory T cells. The transcriptional profile of CD103 T cells demonstrated maintenance of a gene signature similar to circulating T cells along with increased cytokine production and migratory potential. CD103 T cells also expressed genes associated with T cell receptor (TCR) activation and displayed enhanced TCR-mediated reactivation both in vitro and in vivo compared with their CD103 counterparts. These studies reveal the limited recall potential of CD103 T subsets and the role of CD103 T cells as central memory-like T cells within peripheral tissues.