CD8 T cell memory precursors arise early in bone marrow after acute LCMV infection

ROMAGNOLI PA; PREMENKO-LANIER MF; LORIA GD; LEFRANCOIS L; ALTMAN JD

Woods Hole, MA

Conferencia; New England Immunology Conference; 2011

Marine Biology Laboratories

Understanding the mechanism behind the differentiation of memory CD8 T cells is critical to generate protective vaccines against intracellular pathogens. Upon exiting thymus, naiveCD8 T cells migrate mostly through lymphoid tissues where they can be activated in response to infection. The amount and quality of CD8 T cell memory generated in response to an acute infection with an intracellular pathogen is dictated by the signals present in the tissues in which CD8 T cells are activated. Here, we investigated the location, phenotype and functional properties of CD8 T cells responding to acute LCMV infection within different lymphoid tissues.First, we observed that CD8 T cells leave the blood during the first 2 days in response to acute lymphocyticchoriomeningitis virus (LCMV) infection and populate several lymphoid tissues: spleen,peripheral lymph nodes (PLN), mesenteric lymph nodes (MLN) and bone marrow (BM).Second, we find that the phenotype of LCMV-specific CD8 T cells varies with the tissue. Most importantly, CD8 T cells isolated 3 days post infection from BM displayed a memory precursor phenotype, CD62Llo CD25lo Ly6Chi different to the mixed phenotype observed in LCMV-specific CD8 T cells from spleen or PLN at the same time post LCMV infection. Concordantly, we show thatT-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-specificCD8 T cells in PLN and spleen. Finally, we show that the phenotypes observed indifferent tissues correlated with functional properties of LCMV-specific CD8 T cells. We find fewer IFNgamma-producers within the LCMV-specific CD8 T cells in bone marrow than in spleen upon ex vivo stimulation and better memory recall ofCD8 T cells from BM when compared to CD8 T cells from either Spleen or PLN. These findings strongly suggest that CD8 T cell memory precursors can arise in bone marrow early after acute infection with an intracellular pathogen and further investigation is needed to define which environmental signals participate in CD8 T cell memory differentiation in BM.Supported by NIH grants: 1RO1AI042373-04(J.A.) and AI095544 (L.L.)