Human peripheral blood and bone marrow Epstein-Barr virus-specific T-cell repertoire in latent infection reveals distinct memory T-cell subsets

Item Type:	Article
Title:	Human peripheral blood and bone marrow Epstein-Barr virus-specific T-cell repertoire in latent infection reveals distinct memory T-cell subsets
Creators Name:	Guerreiro, M. and Na, I.K. and Letsch, A. and Haase, D. and Bauer, S. and Meisel, C. and Roemhild, A. and Reinke, P. and Volk, H.D. and Scheibenbogen, C.
Abstract:	EBV infection leads to life-long viral persistence. Although EBV infection can result in chronic disease and malignant transformation, most carriers remain disease-free as a result of effective control by T cells. EBV-specific IFN-gamma-producing T cells could be demonstrated in acute and chronic infection as well as during latency. Recent studies, however, provide evidence that assessing IFN-gamma alone is insufficient to assess the quantity and quality of a T-cell response. Using overlapping peptide pools of latent EBV nuclear antigen 1 and lytic BZLF-1 protein and multicolor flow cytometry, we demonstrate that the majority of ex vivo EBV-reactive T cells in healthy virus carriers are indeed IL-2- and/or TNF-producing memory cells, the latter being significantly more frequent in BM. After in vitro expansion, a substantial number of EBV-specific CD4(+) and CD8(+) T cells retained a CC-chemokine receptor 7 (CCR7)-positive memory phenotype. Based on their cytokine profiles, six different EBV-specific T-cell subsets could be distinguished with TNF-single or TNF/IL-2-double producing cells expressing the highest CCR7 levels resembling early-differentiated memory T cells. Our study delineates the memory T-cell profile of a protective immune response and provides a basis for analyzing T-cell responses in EBV-associated diseases.
Keywords:	BM, EBV, Immune Monitoring, Multifunctional T Cells, T-Cell Memory
Source:	European Journal of Immunology
ISSN:	0014-2980
Publisher:	Wiley
Volume:	40
Number:	6
Page Range:	1566-1576
Date:	June 2010
Official Publication:	https://doi.org/10.1002/eji.200940000
PubMed:	View item in PubMed

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