Professional memory CD4+ T lymphocytes preferentially reside and rest in the bone marrow

Immunity. 2009 May;30(5):721-30. doi: 10.1016/j.immuni.2009.03.015. Epub 2009 May 7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Antigens, Ly
  • Integrin alpha2
  • Interleukin-7
  • Ly-6C antigen, mouse