Bone marrow is a major reservoir and site of recruitment for central memory CD8+ T cells

Immunity. 2005 Feb;22(2):259-70. doi: 10.1016/j.immuni.2005.01.008.


Normal bone marrow (BM) contains T cells whose function and origin are poorly understood. We observed that CD8+ T cells in BM consist chiefly of CCR7+ L-selectin+ central memory cells (TCMs). Adoptively transferred TCMs accumulated more efficiently in the BM than naive and effector T cells. Intravital microscopy (IVM) showed that TCMs roll efficiently in BM microvessels via L-, P-, and E-selectin, whereas firm arrest required the VCAM-1/alpha4beta1 pathway. alpha4beta1 integrin activation did not depend on pertussis toxin (PTX)-sensitive Galphai proteins but was reduced by anti-CXCL12. In contrast, TCM diapedesis did not require CXCL12 but was blocked by PTX. After extravasation, TCMs displayed agile movement within BM cavities, remained viable, and mounted potent antigen-specific recall responses for at least two months. Thus, the BM functions as a major reservoir for TCMs by providing specific recruitment signals that act in sequence to mediate the constitutive recruitment of TCMs from the blood.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Bone Marrow / blood supply
  • Bone Marrow / immunology*
  • Bone Marrow / metabolism
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / transplantation
  • Cell Adhesion
  • Cell Movement
  • Cells, Cultured
  • Chemokine CXCL12
  • Chemokines, CXC / metabolism
  • Heterotrimeric GTP-Binding Proteins / metabolism
  • Humans
  • Immunologic Memory / immunology*
  • Integrin alpha4 / metabolism
  • Integrin alpha4beta1 / metabolism
  • Mice
  • Selectins / metabolism
  • Signal Transduction
  • Vascular Cell Adhesion Molecule-1 / metabolism


  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC
  • Cxcl12 protein, mouse
  • Integrin alpha4beta1
  • Selectins
  • Vascular Cell Adhesion Molecule-1
  • Integrin alpha4
  • Heterotrimeric GTP-Binding Proteins