Disruption of the commensal microbiota impairs the maintenance of antigen specific memory T cells 4492

Abstract Description The commensal microbiota that colonizes mucosal surfaces in mammals influence host physiology including immune function, but the mechanisms underlying the microbiota’s influence on systemic immunity remain incompletely understood. The intestinal microbiota has been implicated in the induction of adaptive immune responses in mice and in humans, but it is unknown if long-term maintenance of memory T cells can be influenced by the commensal microbiota. We tested if antigen (ag)-specific CD4+memory Tcells generated in SPF mice could be maintained in SPF mice treated with antibiotics (AB) or in Germ-Free (GF) mice. Using TCR transgenic OT-II cells primed in vivo with their cognate ag, we found that both AB-treated and GF mice failed to maintain transferred memory CD4+T cells when compared to untreated SPF mice. Similarly, CD4+Tcells from SPF mice infected with Influenza/PR8 and adoptively transferred into secondary recipients were maintained in SPF but not in GF or Altered Schaedler’s Flora (ASF) mice. We also found that AB-treated mice failed to maintain lung tissue-resident CD4+ and CD8+ memory T cells generated by immunization with a live-attenuated influenza vaccine (FluMist). Collectively, these finds support the requirement of an intact commensal microbiota for the maintenance of CD4+ memory T cells generated upon infection and vaccination. The mechanisms mediating this effect of the commensal microbiota in memory T cell maintenance are currently under active investigation. Funding Sources NIH- NIAID/NHLBI Grant R01-AI103542 (to G.A.M.), NIH-NIAID Grants R21-AI142306 (To. G.A.M), R01-AI127406 (to D.U., G.A.M. and G.L.), F. Widjaja Foundation IBIRI funds (to G.A.M.), and by the CSMC Dept. of Biomedical Science “Leon Fine Translational Science Award” (to G.A. M.). AAI Intersect Fellowship for Computational Scientists and Immunologists – 2023/2024 Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)