Human bone marrow: a reservoir for "enhanced effector memory" CD8+ T cells with potent recall function.
The role of human bone marrow (BM) CD8+ T cells in the immune response to viral Ags is poorly defined. We report here the identification and characterization of a functionally enhanced effector memory CD8+ T cell population (TEM) in the BM of patients undergoing total joint replacement for osteoarthritis. These BM-derived TEM differ strikingly from correlate cells in peripheral blood (PB), expressing elevated levels of CD27, HLA-DR, CD38, CD69, and unique patterns of chemokine receptors. Interestingly, while BM TEM have low levels of resting perforin and granzyme B, these molecules evidence profound up-regulation in response to TCR stimulation resulting in enhanced cytotoxic potential. Moreover, compared with the TEM subset in PB, BM CD8+ TEM cells demonstrate a more vigorous recall response to pooled viral Ags. Our results reveal that human BM serves as a repository for viral Ag-specific TEM with great therapeutic potential in vaccine development.
Zhang
Xiaoyu
X
Department of Otorhinolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201-1619, USA.
Dong
Haidong
H
Lin
Wei
W
Voss
Stephen
S
Hinkley
Lucinda
L
Westergren
Melissa
M
Tian
Guoliang
G
Berry
Daniel
D
Lewellen
David
D
Vile
Richard G
RG
Chen
Lieping
L
Farber
Donna L
DL
Strome
Scott E
SE
D000368:Aged; D000956:Antigens, Viral / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D003587:Cytomegalovirus / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D019707:Receptors, Chemokine / Q000096:biosynthesis
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D019707:Receptors, Chemokine