title: Human bone marrow as a source to generate CMV-specific CD4+ T cells with multifunctional capacity.
abstract: The bone marrow (BM) is an important compartment for T cell memory. In cytomegalovirus (CMV)-seropositive individuals peripheral blood (PB) CMV-specific T cells constitute a large fraction of PB T cells but are mostly differentiated effector/effector memory T cells with limited survival and proliferative potential. In this study, we performed a comprehensive analysis of the CMV-specific T cell response in BM studying both CD4+ and CD8+ T cell responses against overlapping peptide pools of the CMV proteins pp65 and immediate early protein-1. CMV-specific T cell responses were characterized ex vivo and after in vitro expansion of paired PB/BM samples by multiparameter flow cytometry determining surface phenotype, cytokine profile, and cytotoxic capability. Comparable frequencies of CMV-specific T cells were found in un-manipulated PB and BM. Both total CD4+ and CD8+ T cells could be more rapidly expanded from BM. Expanded BM T cells contained significantly higher frequencies of CMV-specific CD4+ T cells than PB. Furthermore, higher frequencies of specific CD4+ T cells from BM were multifunctional, characterized by simultaneous production of interferon-gamma, tumor necrosis factor, and interleukin-2. Use of BM may thus facilitate more rapid generation of adoptive T cells with enhanced functionality.
authors.affiliation: Department of Hematology and Oncology, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Il-Kang
authors.initials: IK
authors.lastname: Na
authors.forename: Anne
authors.initials: A
authors.lastname: Letsch
authors.forename: Manuel
authors.initials: M
authors.lastname: Guerreiro
authors.forename: Sandra
authors.initials: S
authors.lastname: Bauer
authors.forename: Ines
authors.initials: I
authors.lastname: Noack
authors.forename: Jens
authors.initials: J
authors.lastname: Geginat
authors.forename: Petra
authors.initials: P
authors.lastname: Reinke
authors.forename: Michael
authors.initials: M
authors.lastname: Loesch
authors.forename: Heino
authors.initials: H
authors.lastname: Kienapfel
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; D000956:Antigens, Viral / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology* / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D015550:Cell Degranulation / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology*; D008875:Middle Aged; D010455:Peptides / Q000276:immunology; D010750:Phosphoproteins / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D010455:Peptides; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa