PROJECT SUMMARY/ABSTRACTT cells expressing the gamma delta T cell receptor (?? T cells) are strategically located at mucosal barriers suchas the gastrointestinal tract. As such, ?? T cells are thought to be ideally placed for rapid immunity to pathogensand are also thought to be a critical component of innate immunity and epithelial barrier integrity, both of whichbecome compromised in the elderly. Even though many clinically relevant human pathogens, such as Listeriamonocytogenes (LM), invade through the intestinal mucosa of the elderly, our understanding of intestinal T cellresponses to relevant pathogens or vaccinations in these populations remains incomplete. We have recentlyidentified a subset of protective long-lived memory ?? T cells after oral but not intravenous immunization thatresemble memory ?? T cells described in humans. Surprisingly, this pathogen-elicited memory ?? T cell responseis enhanced in aged mice and is associated with an enhanced antigen-specific CD8 T cell response. Thus, thecentral aim of this proposal is to determine the role and protective potential of pathogen-elicited memory?? T cells in aged mice. This proposal will test the central hypothesis that pathogen-elicited memory ?? T cellsprovide help to the adaptive immune response in aged mice. In the aims outlined below, the aged response afteroral immunization will be explored. Additionally, whether memory ?? T cells provide help to CD8 T cells in agedmice will be determined.Specific Aim 1: Evaluate the LM-elicited adaptive T cell response in aged mice after oral LMimmunization.Specific Aim 2: Evaluate LM-elicited adaptive ?? T cells contribution to protective immunity in aged mice.Although in the past few years' substantial progress has been made in our understanding of the mucosal immuneresponse in the intestine, serious gaps in our knowledge remain. Many studies utilize non-physiologic infectionroutes to study immune responses to mucosal pathogens but models that more closely reproduce the humancondition are needed. The goal of this proposed study is to understand mechanisms regulating enhancedpathogen-elicited T cell responses in aged mice after oral immunization. This is highly significant for inducingprotective immunity and developing successful vaccination strategies in the elderly population and could lead tosignificant advances concerning the manipulation of immunity in aged individuals.