Generation and maintenance of antigen-specific CD8 T cells in the vaginal mucosa following systemic versus mucosal routes of immunization (41.6)

Abstract

Abstract In this study we compared the efficacy of two different routes of viral infection on the generation, maintenance, and localization of antigen specific CD8T cells in lymphoid, non-lymphoid, and mucosal tissues during peak effector and memory phases of an immune response. We used an adoptive transfer system of naïve transgenic CD8 T cells, followed by intra-peritoneal (i.p) or intra-nasal (i.n) LCMV infection. Surprisingly, on day 8 the peak of the primary response, i.p. infection resulted in higher numbers of antigen-specific CD8T cells in the vaginal mucosa and ILN only, in addition to 2–3x more antigen specific CD8 T cells that co-expressed both IFNγ and TNFα, when compared to the i.n. route of infection. During memory, equivalent numbers of antigen specific CD8T cells were detected at all sites, irrespective of the route of infection. Following intravaginal re-challenge, both i.p. and i.n generated memory CD8 T cells showed robust secondary responses in the vaginal tract, however the i.n. memory CD8 T cell response was consistently greater. These data suggest that both systemic and mucosal routes of infection can generate a similar quantity of memory CD8 T cells in mucosal sites. However, the initial route of infection appears to influence the programming of the memory CD8T cells generated, and these early differences in priming may impact the quality of protective secondary responses.