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 (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.
Mazo
Irina B
IB
Department of Pathology, The CBR Institute for Biomedical Research, Harvard Medical School, Boston, Massachusetts 02215, USA.
Honczarenko
Marek
M
Leung
Harry
H
Cavanagh
Lois L
LL
Bonasio
Roberto
R
Weninger
Wolfgang
W
Engelke
Katharina
K
Xia
Lijun
L
McEver
Rodger P
RP
Koni
Pandelakis A
PA
Silberstein
Leslie E
LE
von Andrian
Ulrich H
UH
D019264:Adoptive Transfer; D000818:Animals; D001853:Bone Marrow / Q000098:blood supply / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D039441:Integrin alpha4 / Q000378:metabolism; D039041:Integrin alpha4beta1 / Q000378:metabolism; D051379:Mice; D019087:Selectins / Q000378:metabolism; D015398:Signal Transduction; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D039041:Integrin alpha4beta1; D019087:Selectins; D019010:Vascular Cell Adhesion Molecule-1; D039441:Integrin alpha4; D020962:Heterotrimeric GTP-Binding Proteins