Secondary infections rejuvenate the intestinal CD103+ tissue-resident memory T cell pool

Sci Immunol. 2022 Nov 11;7(77):eabp9553. doi: 10.1126/sciimmunol.abp9553. Epub 2022 Nov 4.

Abstract

Resident T lymphocytes (TRM) protect tissues during pathogen reexposure. Although TRM phenotype and restricted migratory pattern are established, we have a limited understanding of their response kinetics, stability, and turnover during reinfections. Such characterizations have been restricted by the absence of in vivo fate-mapping systems. We generated two mouse models, one to stably mark CD103+ T cells (a marker of TRM cells) and the other to specifically deplete CD103- T cells. Using these models, we observed that intestinal CD103+ T cells became activated during viral or bacterial reinfection, remained organ-confined, and retained their original phenotype but failed to reexpand. Instead, the population was largely rejuvenated by CD103+ T cells formed de novo during reinfections. This pattern remained unchanged upon deletion of antigen-specific circulating T cells, indicating that the lack of expansion was not due to competition with circulating subsets. Thus, although intestinal CD103+ resident T cells survived long term without antigen, they lacked the ability of classical memory T cells to reexpand. This indicated that CD103+ T cell populations could not autonomously maintain themselves. Instead, their numbers were sustained during reinfection via de novo formation from CD103- precursors. Moreover, in contrast to CD103- cells, which require antigen plus inflammation for their activation, CD103+ TRM became fully activated follwing exposure to inflammation alone. Together, our data indicate that primary CD103+ resident memory T cells lack secondary expansion potential and require CD103- precursors for their long-term maintenance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes
  • Coinfection*
  • Immunologic Memory*
  • Inflammation
  • Memory T Cells
  • Mice
  • Reinfection