Circulating memory CD8 + T cells are limited in forming CD103 + tissue-resident memory T cells at mucosal sites after reinfection.

Tissue-resident memory CD8 ⁺ T cells (T _RM ) localize to barrier tissues and mediate local protection against reinvading pathogens. Circulating central memory (T _CM ) and effector memory CD8 ⁺ T cells (T _EM ) also contribute to tissue recall responses, but their potential to form mucosal T _RM remains unclear. Here, we employed adoptive transfer and lymphocytic choriomeningitis virus reinfection models to specifically assess secondary responses of T _CM and T _EM at mucosal sites. Donor T _CM and T _EM exhibited robust systemic recall responses, but only limited accumulation in the small intestine, consistent with reduced expression of tissue-homing and -retention molecules. Murine and human circulating memory T cells also exhibited limited CD103 upregulation following TGF-β stimulation. Upon pathogen clearance, T _CM and T _EM readily gave rise to secondary T _EM . T _CM also formed secondary central memory in lymphoid tissues and T _RM in internal tissues, for example, the liver. Both T _CM and T _EM failed to substantially contribute to resident mucosal memory in the small intestine, while activated intestinal T _RM , but not liver T _RM , efficiently reformed CD103 ⁺ T _RM . Our findings demonstrate that circulating T _CM and T _EM are limited in generating mucosal T _RM upon reinfection. This may pose important implications on cell therapy and vaccination strategies employing memory CD8 ⁺ T cells for protection at mucosal sites.
(© 2020 Wiley-VCH GmbH.)