TY - JOUR
T1 - Bone marrow is a major reservoir and site of recruitment for central memory CD8+ T cells
AU - Mazo, Irina B.
AU - Honczarenko, Marek
AU - Leung, Harry
AU - Cavanagh, Lois L.
AU - Bonasio, Roberto
AU - Weninger, Wolfgang
AU - Engelke, Katharina
AU - Xia, Lijun
AU - McEver, Rodger P.
AU - Koni, Pandelakis A.
AU - Silberstein, Leslie E.
AU - Von Andrian, Ulrich H.
N1 - Funding Information:
We thank Guiying Cheng and Bruce Reinhardt for technical support, Joe Moore for editorial assistance, and Jean-Marc Gauguet for helpful discussions. This work was supported by National Institutes of Health grants AI061663, HL62524, HL54936, and HL56949 to U.H.v.A. and a T32 grant in Transfusion Medicine from Children’s Hospital, Boston (HL66987), the Amy Potter fellowship, and a grant from the Charles Hood Foundation to I.B.M.
PY - 2005/2
Y1 - 2005/2
N2 - 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 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 T CMs by providing specific recruitment signals that act in sequence to mediate the constitutive recruitment of TCMs from the blood.
AB - 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 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 T CMs by providing specific recruitment signals that act in sequence to mediate the constitutive recruitment of TCMs from the blood.
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U2 - 10.1016/j.immuni.2005.01.008
DO - 10.1016/j.immuni.2005.01.008
M3 - Article
C2 - 15723813
AN - SCOPUS:13844272211
SN - 1074-7613
VL - 22
SP - 259
EP - 270
JO - Immunity
JF - Immunity
IS - 2
ER -