Bone Marrow Is a Major Reservoir and Site of Recruitment for Central Memory CD8 + T Cells

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 (T CMs). Adoptively transferred T CMs accumulated more efficiently in the BM than naive and effector T cells. Intravital microscopy (IVM) showed that T CMs roll efficiently in BM microvessels via L-, P-, and E-selectin, whereas firm arrest required the VCAM-1/α4β1 pathway. α4β1 integrin activation did not depend on pertussis toxin (PTX)-sensitive Gαi proteins but was reduced by anti-CXCL12. In contrast, T CM diapedesis did not require CXCL12 but was blocked by PTX. After extravasation, T CMs 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 T CMs by providing specific recruitment signals that act in sequence to mediate the constitutive recruitment of T CMs from the blood.