| Abstrakt: |
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. CD103 tracker: Tissue-resident memory T (TRM) cells protect against tissue-specific infections, yet how they act during secondary infections is incompletely understood. Here, von Hoesslin et al. generated two mouse models, one allowing for the tracking of CD103+ TRM cells and one that specifically deleted all CD103− cells. With these models, the authors established that although preprimed CD103+ TRM cells became highly activated during secondary intestinal infection, they did not expand, leave the tissue, or change phenotype. Instead, CD103− precursor T cells expanded and seeded new CD103+ TRM cells in the intestinal tissue. CD103+ TRM cells were activated in the presence of inflammation alone, whereas CD103− precursors required inflammation and antigen. Thus, CD103− cells replenish the CD103+ TRM cell population in intestinal tissue during secondary infection. [ABSTRACT FROM AUTHOR] |
