CD103 expression distinguishes subpopulations of naïve CD8+ T cells that are modulated by the microbiome and are pre-programmed to different memory phenotypes 3964

Abstract Description The population of naïve T cells is heterogeneous, and one of the fundamental questions in immunology is whether naïve T cells are pre-programmed to differentiate into subsets of effector and memory T cells. We found that E-Cadherin receptor CD103 is expressed on 65-75% of CD44Lo CD8+ T cells in spleen of specific-pathogen-free (SPF) C57BL/6 mice. As compared to SPF mice, there was ∼10% reduction in the CD103+ subset in spleen of germ-free (GF) mice, but the percentages of this subset remained unaltered in Dirty mice (SPF mice exposed to Pet Store mice). Single-cell RNAseq of splenic CD8+ T cells revealed subpopulations of Itgae (encodes CD103)-expressing naïve CD8+ T cells in both SPF and GF mice, but an unique cell cluster was only present in the SPF mice. This cluster is enriched for genes related to T cell proliferation, activation and signal transduction. We hypothesized that CD103+ and CD103- naïve T cells are pre-programmed for distinct effector and/or memory cell fates during an immune response. During an acute infection with lymphocytic choriomeningitis virus (LCMV), memory CD8+ T cells derived from CD103+ naïve CD8+ T cells expressed higher levels of CD27 and CXCR3 and lower amounts of Granzyme B and CX3CR1. Overall, these results suggest that CD103+ naïve CD8+ T cells might be pre-programmed to a central memory fate in LCMV infection, and the microbiome may modulate the differentiation trajectory of naïve CD8+ T cells. Funding Sources Supported by NIH/NIAID 5R21AI173757-02; NLM 5T15LM007359-23 Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)