CD8 T cells are rapidly recruited to both immunized and unimmunized skin after vaccinica virus skin scarification persist long-term as nonmigratory resident memory T cells (Trm), and provide rapid, effective, and specific local immunity

Abundant Trm populate normal, non-inflamed skin in both humans and mice, but little is known about their trafficking patterns. We created parabiotic mice by joining wild-type (WT) mice with GFP-transgenic mice. These mice rapidly developed a shared a circulatory system, with equilibration of GFP+ and GFP- T cells in blood and lymphoid tissues (LT), but this never occurred in skin. To test the trafficking of CD8 Trm, we s.s. immunized OT-1 bearing mice with VACV that expressed ovalbumin (VACV-OVA). Five weeks after s.s., we joined these mice parabiotically with naive mice. After 2 weeks, central memory (Tcm) OT-1 cells had equilibrated in blood and LT. However, OT-1 skin Trm could only be detected in the immunized parabiont, even after 24 weeks of parabiosis. When B-cell-deficient (µMT) mice for parabiosis (both immunized and naïve), we found that the skin of the immunized but not the naïve mouse rapidly cleared virus on challenge. These data suggest that CD8+ Trm can persist in previously infected skin and do not readily migrate out of skin. Next we asked whether uninfected skin of immunized mice contained OT-1 Trm. We could find substantial numbers of OT-1 Trm cells in uninfected skin; this number increased further after multiple infections. VACV was rapidly cleared from uninfected skin of s.s. immunized mice after challenge. Our results demonstrate that CD8+ Trm cells persist long term in the skin of s.s. immunized mice and provide rapid and site specific protection.