CMV-specific central memory T cells reside in bone marrow.
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.
Letsch
Anne
A
Department of Hematology, Oncology, Charité, Berlin, Germany.
Knoedler
Maren
M
Na
Il-Kang
IK
Kern
Florian
F
Asemissen
Anne-Marie
AM
Keilholz
Ulrich
U
Loesch
Michael
M
Thiel
Eckhard
E
Volk
Hans-Dieter
HD
Scheibenbogen
Carmen
C
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
D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa