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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 alpha2. Antigen-specific memory CD4(+) T lymphocytes highly expressed Ly-6C, unlike most splenic CD44(hi)CD62L(-) CD4(+) T lymphocytes. In adult mice, more than 80% of Ly-6C(hi)CD44(hi)CD62L(-) 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.

Original publication

DOI

10.1016/j.immuni.2009.03.015

Type

Journal

Immunity

Publication Date

05/2009

Volume

30

Pages

721 - 730

Keywords

Animals, Antigens, Ly, B-Lymphocytes, Bone Marrow, CD4-Positive T-Lymphocytes, Down-Regulation, Gene Expression, Immunologic Memory, Integrin alpha2, Interleukin-7, Mice, Oligonucleotide Array Sequence Analysis, Stromal Cells