Abstract

Abstract The amount and quality of CD8 T cell memory generated in response to an acute infection with an intracellular pathogen is influenced by the signals present in the tissues in which CD8 T cells are activated. Here, we investigated if location dictates the phenotype and functional properties of CD8 T cells responding to acute lymphocytic choriomeningitis virus (LCMV) infection in different lymphoid tissues. First, we show that CD8 T cells isolated 3 days post infection (p.i.) from bone marrow (BM) displayed a memory precursor phenotype, CD62LloCD25loLy6Chi different to the phenotype observed in LCMV-specific CD8 T cells from spleen or peripheral lymph nodes (PLN). Second, we show that T-bet, a T-box transcription factor found predominantly in terminally differentiated effector CD8 T cells, is almost absent in LCMV-specific CD8 T cells from BM in contrast to the high T-bet expression found on LCMV-specific CD8 T cells from PLN and spleen. Differences in T-bet are also detected after acute infection with vesicular stomatitis virus and L. monocytogenes. Finally, we find that CD8 T cells from BM recall better upon secondary challenge when compared to CD8 T cells from spleen or PLN. These findings strongly suggest that CD8 T cell memory precursors can arise in BM early after acute infection with an intracellular pathogen and further investigation is needed to define the environmental signals influencing CD8 T cell memory differentiation.

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