Progressive differentiation of memory CD8 T cells in the cervicovaginal tissue

The memory CD8 T cell compartment in human cervicovaginal tissue (CVT) is phenotypically and functionally distinct compared to other non-lymphoid tissues. To determine if these distinctive features are driven by residence in the tissue itself, rather than a consequence of local antigenic insults, we used a mouse model to assess memory CD8 T cell differentiation in the CVT. Following systemic immunization to elicit a CD8 T cell response to a herpes simplex virus (HSV) epitope, HSV-specific memory CD8 T cells were stably maintained in other tissues but gradually declined in the CVT over 5 months post-immunization, correlating with a delay in viral control upon HSV challenge. While memory cells in the periphery and small intestine maintained a fairly stable phenotype after 30 days, memory CD8 T cells in the CVT gradually acquired a CD103+, TCF-1-, granzyme B+ phenotype over the 5 month time span. Notably, a sizable and phenotypically similar population of CD8 T cells was also found in human CVT. Our data indicate that the CVT environment itself considerably affects memory CD8 T cell maintenance and differentiation, and call for a reassessment of the prevalent model of memory T cell maintenance which does not currently account for tissue-specific divergence.