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

Abstract

Tissue-resident memory T (T RM ) cells remain poised in the tissue and mediate robust protection from secondary infection. T RM cells within the intestine and other tissues are heterogeneous in their phenotype and function; however, the contributions of these T RM subsets to secondary infection remain poorly defined. To address the plasticity of intestinal T RM subsets and their role in local and systemic immunity, we generated mice to fate map intestinal CD103 + T RM cells and track their location and function during secondary infection with Yersinia pseudotuberculosis . We found that CD103 + T RM cells remained lodged in the tissue and were poorly reactivated during secondary challenge. CD103 − T RM 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 RM cells demonstrated maintenance of a gene signature similar to circulating T cells along with increased cytokine production and migratory potential. CD103 − T RM 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 RM subsets and the role of CD103 − T RM cells as central memory–like T cells within peripheral tissues.

Single-cell profiling reveals pathogenic role and differentiation trajectory of granzyme K+CD8+ T cells in primary Sjögren’s syndrome

“…CD8 + TRM cells within a variety of tissue compartments are heterogeneous in phenotype and function, and can be broadly divided into two subpopulations based on CD103 expression: CD69 + CD103 -CD8 + TRM (CD103n CD8 + TRM) and CD69 + CD103 + CD8 + TRM (CD103p CD8 + TRM) cells (11). Some tissues, such as intestinal and salivary gland, harbor both CD103p and CD103n CD8 + TRM subsets, and these two populations displayed distinct functional capabilities in the context of response to infection (12)(13)(14). However, the characteristics differences of these TRM subsets and their contributions in pSS remain poorly defined.…”

Sepsis-induced changes in differentiation, maintenance, and function of memory CD8 T cell subsets

“…and Fung et al. showed that CD103 + T RM cells have limited proliferation capacity, but CD103 - T RM cells undergo robust expansion upon Ag re-encounter, further highlighting the heterogeneity within T RM pool ( 121 , 122 ). Nonetheless, successive Ag exposures improve the longevity and protective function of T RM pool; for example, 4° influenza-specific T RM cells show enhanced durability and heterosubtypic immunity than 1° T RM cells ( 123 ).…”

Advances and challenges in studying the tissue‐resident T cell compartment in the human female reproductive tract

“…A set of recent mouse model studies used elegant fate-mapping approaches to assess how intestinal T RM respond to TCR-mediated reactivation. 84,85 These CD8 T-cell-focused studies found that CD103+ T RM cells had fairly limited responses to TCRmediated reactivation. We hypothesize that a similar level of T RM hyporesponsiveness may exist in the FRT, helping to maintain T RM homeostasis during inflammatory episodes.…”

“…Of note, this baseline level of inflammation appears to be critical for maintenance of barrier immunity (“inflammatory surveillance”). A set of recent mouse model studies used elegant fate‐mapping approaches to assess how intestinal T RM respond to TCR‐mediated reactivation 84,85 . These CD8 T‐cell‐focused studies found that CD103+ T RM cells had fairly limited responses to TCR‐mediated reactivation.…”