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  • Title: Human bone marrow as a source to generate CMV-specific CD4+ T cells with multifunctional capacity.
    Author: Na IK, Letsch A, Guerreiro M, Bauer S, Noack I, Geginat J, Reinke P, Loesch M, Kienapfel H, Thiel E, Volk HD, Scheibenbogen C.
    Journal: J Immunother; 2009; 32(9):907-13. PubMed ID: 19816191.
    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.
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