Oral infection drives a distinct population of intestinal resident memory cd8⁺ t cells with enhanced protective function

The intestinal mucosa promotes Tcell responses that might be beneficial for effective mucosal vaccines. However, intestinal resident memory T (Trm) cell formation and function are poorly understood. We found that oral infection with Listeria monocytogenes induced a robust intestinal CD8 Tcell response and blocking effector Tcell migration showed that intestinal Trm cells were critical for secondary protection. Intestinal effector CD8 Tcells were predominately composed of memory precursor effector cells (MPECs) that rapidly upregulated CD103, which was needed for Tcell accumulation in the intestinal epithelium. CD103 expression, rapid MPEC formation, and maintenance in intestinal tissues were dependent on Tcell intrinsic transforming growth factor β signals. Moreover, intestinal Trm cells generated after intranasal or intravenous infection were less robust and phenotypically distinct from Trm cells generated after oral infection, demonstrating the critical contribution of infection route for directing the generation of protective intestinal Trm cells.