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

IB Mazo, M Honczarenko, H Leung, LL Cavanagh… - Immunity, 2005 - cell.com
IB Mazo, M Honczarenko, H Leung, LL Cavanagh, R Bonasio, W Weninger, K Engelke…
Immunity, 2005cell.com
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/α4β1
pathway. α4β1 integrin activation did not depend on pertussis toxin (PTX)-sensitive Gαi …
Summary
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/α4β1 pathway. α4β1 integrin activation did not depend on pertussis toxin (PTX)-sensitive Gαi 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.
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