Professional Memory CD4+ T Lymphocytes Preferentially Reside and Rest in the Bone Marrow.
Tokoyoda, Koji 1,*; Zehentmeier, Sandra 1; Hegazy, Ahmed N. 1,2; Albrecht, Inka 1; Grun, Joachim R. 1; Lohning, Max 1,2; Radbruch, Andreas 1
[Article] Immunity. 30(5):721-730, May 2009.

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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 [alpha]2. Antigen-specific memory CD4 T lymphocytes highly expressed Ly-6C, unlike most splenic CD44hiCD62L- CD4 T lymphocytes. In adult mice, more than 80% of Ly-6ChiCD44hiCD62L- 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.

(C) 2009Elsevier, Inc.