Professional Memory CD4 + T Lymphocytes Preferentially Reside and Rest in the Bone Marrow

CD4 + T lymphocytes are key to immunological memory. Here we show that in the memory phase of specific immune responses, most of the memory CD4 + T lymphocytes had relocated into the bone marrow (BM) within 3–8 weeks after their generation—a process involving integrin α2. Antigen-specific memory CD4 + T lymphocytes highly expressed Ly-6C, unlike most splenic CD44 hiCD62L − CD4 + T lymphocytes. In adult mice, more than 80% of Ly-6C hiCD44 hiCD62L − memory CD4 + T lymphocytes were in the BM. In the BM, they associated to IL-7-expressing VCAM-1 + stroma cells. Gene expression and proliferation were downregulated, indicating a resting state. Upon challenge with antigen, they rapidly expressed cytokines and CD154 and efficiently induced the production of high-affinity antibodies by B lymphocytes. Thus, in the memory phase of immunity, memory helper T cells are maintained in BM as resting but highly reactive cells in survival niches defined by IL-7-expressing stroma cells.