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Human bone marrow as a source to generate CMV-specific CD4+ T cells with multifunctional capacity

Item Type:Article
Title:Human bone marrow as a source to generate CMV-specific CD4+ T cells with multifunctional capacity
Creators Name:Na, I.K. and Letsch, A. and Guerreiro, M. and Bauer, S. and Noack, I. and Geginat, J. and Reinke, P. and Loesch, M. and Kienapfel, H. and Thiel, E. and Volk, H.D. and Scheibenbogen, C.
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.
Keywords:Multifunctional T Cells, CD4, CMV
Source:Journal of Immunotherapy
Publisher:Lippincott Williams & Wilkins
Page Range:907-913
Date:November 2009
Official Publication:https://doi.org/10.1097/CJI.0b013e3181b7be60
PubMed:View item in PubMed

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