Selective accumulation of virus-specific CD8+ T cells with unique homing phenotype within the human bone marrow.
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 Epstein-Barr virus (EBV) lytic antigens were enriched 3-fold in marrow compared with blood, whereas the response to EBV latent epitopes was equivalent between the 2 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 cytomegalo-virus (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 with CMV-specific populations. These observations identify a novel bone marrow homing phenotype for CD8(+) memory T cells, which necessitates a reevaluation of the magnitude of antigen-specific populations within the lymphoid system.
Palendira
Umaimainthan
U
Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham, United Kingdom.
Chinn
Rosanna
R
Raza
Wajid
W
Piper
Karen
K
Pratt
Guy
G
Machado
Lee
L
Bell
Andrew
A
Khan
Naeem
N
Hislop
Andrew D
AD
Steyn
Richard
R
Rickinson
Alan B
AB
Buckley
Christopher D
CD
Moss
Paul
P
D001853:Bone Marrow / Q000378:metabolism / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D002465:Cell Movement; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D008954:Models, Biological; D010641:Phenotype; D019713:Receptors, CCR5 / Q000378:metabolism; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism; D019562:Viral Load
C106330:CXCR6 protein, human; D018925:Chemokines; D016207:Cytokines; D019713:Receptors, CCR5; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D011991:Receptors, Virus; D007371:Interferon-gamma