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* Department of Otorhinolaryngology–Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201;
Department of Immunology, Mayo Clinic College of Medicine, Rochester MN 55905;
Department of Otorhinolaryngology–Head and Neck Surgery, Mayo Clinic College of Medicine, Rochester MN 55905;
Division of Biostatistics, University of Maryland Greenebaum Cancer Center, Baltimore, MD 21201;
¶ Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester MN 55905;
|| Department of Molecular Medicine, Mayo Clinic College of Medicine, Rochester MN 55905;
# Department of Dermatology, Johns Hopkins University, Baltimore, MD 21231; and
** Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 X.Z. effort was supported by a Postdoctoral Head and Neck Cancer Research Fellowship in honor of Richard H. Stoll.
2 Address correspondence and reprint requests to Dr. Scott E. Strome, Department of Otorhinolaryngology–Head and Neck Surgery, University of Maryland School of Medicine, 16 South Eutaw Street, Suite 500, Baltimore, MD 21201-1619. E-mail address: sstrome{at}smail.umaryland.edu
3 Abbreviations used in this paper: TEM, effector memory T; TCM, central memory T; BM, bone marrow; PB, peripheral blood; BMC, BM cell; CEF, CMV, Epstein-Barr virus and influenza virus; OA, osteoarthritis.
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