Molecular characterization of survival niches for memory T helper cells in bone marrow

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Recently, I have described that in distinct murine immune responses memory T helper (Th) cells preferentially if not exclusively reside and rest in the bone marrow (BM). CD4 T cells after activation in secondary lymphoid organs (SLOs) immigrate into the BM in a CD69- and CD49b (a collagen receptor)-dependent manner and localize as memory Th cells, expressing Ly-6C and CD44, to survival niches organized by collagen XI+IL-7+ stromal cells of the BM. The molecules mediating the survival and residency of memory Th cells in the BM are not known. The project proposed aims at the identification of cytokines, chemokines and adhesion molecules involved in the maintenance of memory Th cells in the BM. In particular, I will (i) determine the roles of the CD49b and its ligand collagen XI, and of IL-7 and its receptor, and (ii) identify other factors involved in the maintenance of memory Th cells. This project will achieve a molecular understanding of how the memory Th cells are kept in quiescence and survive in their BM niches, in the apparent absence of antigen.