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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 …