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Blood, 15 October 2008, Vol. 112, No. 8, pp. 3293-3302.
Prepublished online as a Blood First Edition Paper on July 17, 2008; DOI 10.1182/blood-2008-02-138040.
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Submitted February 11, 2008
Accepted June 30, 2008
Selective accumulation of virus-specific CD8+ T cells with unique homing phenotype within the human bone marrow
Umaimainthan Palendira, Rosanna Chinn, Wajid Raza, Karen Piper, Guy Pratt, Lee Machado, Andrew Bell, Naeem Khan, Andrew D Hislop, Richard Steyn, Alan B Rickinson, Christopher D. Buckley, and Paul Moss*
Immunology and Inflammation program, Garvan Institute, Sydney, Australia
Department of Cancer Studies, CRUK Institute for Cancer Studies, Birmingham, United Kingdom
Department of Cancer Studies, Heartlands Hospital, Birmingham, United Kingdom
Medical Research Council Centre for Immune Regulation, University of Birmingham, Birmingham, United Kingdom
* Corresponding author; email: p.moss{at}bham.ac.uk.
The bone marrow plays a unique role within the immune system. We compared the phenotype and function of virus-specific CD8+ T cells from matched samples of human peripheral blood and bone marrow. Analysis of virus-specific memory CD8+ T cells showed widely divergent partition of antigen-specific populations between blood and bone marrow. T cells specific for EBV lytic antigens were enriched three fold in marrow compared to blood whereas the response to EBV latent epitopes was equivalent between the two compartments. No difference in EBV viral load or expression of the EBV lytic protein was observed between blood and bone marrow. In direct contrast, although CMV-specific T cells were the largest virus-specific population within peripheral blood they were reduced by 60% within marrow. Bone marrow T cells were found to exhibit a unique CCR5+CXCR6+CXCR3- homing phenotype which has not been observed on T cells from other secondary lymphoid organs or peripheral organs. Expression of CCR5 and CXCR6 was higher on EBV-specific T cells within peripheral blood compared to CMV-specific populations. These observations identify a novel bone marrow homing phenotype for CD8+ memory T cells, which necessitates a re-evaluation of the magnitude of antigen-specific populations within the lymphoid system.
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