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

Irina B. Mazo, Marek Honczarenko, Harry Leung, Lois L. Cavanagh, Roberto Bonasio, Wolfgang Weninger, Katharina Engelke, Lijun Xia, Rodger P. McEver, Pandelakis A. Koni, Leslie E. Silberstein, Ulrich H. Von Andrian

Research output: Contribution to journalArticle

271 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)259-270
Number of pages12
JournalImmunity
Volume22
Issue number2
DOIs
StatePublished - Feb 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Mazo, I. B., Honczarenko, M., Leung, H., Cavanagh, L. L., Bonasio, R., Weninger, W., Engelke, K., Xia, L., McEver, R. P., Koni, P. A., Silberstein, L. E., & Von Andrian, U. H. (2005). Bone marrow is a major reservoir and site of recruitment for central memory CD8+ T cells. Immunity, 22(2), 259-270. https://doi.org/10.1016/j.immuni.2005.01.008