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

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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., Letsch, A., Guerreiro, M., Bauer, S., Noack, I., Geginat, J., Reinke, P., Loesch, M., Kienapfel, H., Thiel, E., 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
ISSN:	1524-9557
Publisher:	Lippincott Williams & Wilkins
Volume:	32
Number:	9
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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