Circulating memory CD8 <sup>+</sup> T cells are limited in forming CD103 <sup>+</sup> tissue‐resident memory T cells at mucosal sites after reinfection
Felix M. Behr, Ammarina Beumer‐Chuwonpad, Natasja A. M. Kragten, Thomas H. Wesselink, Regina Stark, Klaas P. J. M. van Gisbergen
Abstract
Abstract 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.