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(CM)s). Adoptively transferred T(CM)s accumulated more efficiently in the BM than naive and effector T cells. Intravital microscopy (IVM) showed that T(CM)s 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, T-CM diapedesis did not require CXCL12 but was blocked by PTX. After extravasation, T(CM)s 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(CM)s by providing specific recruitment signals that act in sequence to mediate the constitutive recruitment of T(CM)s from the blood.