Authors: Madlaina von Hoesslin, Miriam Kuhlmann, Gustavo Pereira de Almeida, Kristiyan Kanev, Christine Wurmser, Ann-Katrin Gerullis, Patrick Roelli, Jacqueline Berner, Dietmar Zehn
Published: 2022-11-04
DOI: 10.1126/sciimmunol.abp9553
Source: Full article
Resident T lymphocytes (TRM) protect tissues during pathogen reexposure. Although TRMphenotype 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 TRMcells) 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+TRMbecame 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.