title: CMV-specific central memory T cells reside in bone marrow.
abstract: CMV-specific CD8(+) T cell responses in peripheral blood (PB) are characterized by a preponderance of effector and effector memory T cells. CMV-specific central memory T cells (T(CM)), which are considered crucial in maintaining long-term immunity, are rarely detectable in PB. In this study we have analyzed differentiation and function of CMV pp65-specific CD8(+) T cells in paired samples of human PB and BM using intracellular cytokine and tetramer staining. Overall frequencies of CMV pp65-specific T cells were similar in PB compared to BM; however, CMV-specific CD45RA(-)CCR7(+) T(CM) were almost exclusively detectable in BM, which was not related to a general accumulation of T(CM) in BM. In vitro, CMV-specific T cells could be more efficiently expanded from BM (median 128-fold, n=6) than from PB (median 72-fold, p=0.01). Taken together, these data show that the BM is a compartment harboring CMV-specific T(CM) and underline the concept of the BM as a secondary immune organ. CMV specific BM-derived T(CM) might be a valuable source for generating T cells for adoptive transfer.
authors.affiliation: Department of Hematology, Oncology, Charité, Berlin, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Letsch
authors.forename: Maren
authors.initials: M
authors.lastname: Knoedler
authors.forename: Il-Kang
authors.initials: IK
authors.lastname: Na
authors.forename: Florian
authors.initials: F
authors.lastname: Kern
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Asemissen
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keilholz
authors.forename: Michael
authors.initials: M
authors.lastname: Loesch
authors.forename: Eckhard
authors.initials: E
authors.lastname: Thiel
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Carmen
authors.initials: C
authors.lastname: Scheibenbogen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology
chemical_list: D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa