JVI Accepts, published online ahead of print on 18 March 2009
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J. Virol. doi:10.1128/JVI.00106-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

DIFFERENTIAL EFFECT OF HHV-6A ON CELL DIVISION AND APOPTOSIS AMONG NAÏVE, AND CENTRAL AND EFFECTOR MEMORY CD4+ AND CD8+ T CELL SUBSETS

Sudhir Gupta*, Sudhanshu Agrawal, and Sastry Gollapudi

Division of Basic and Clinical Immunology, University of California, Irvine, California

* To whom correspondence should be addressed. Email: sgupta{at}uci.edu.


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Abstract

Immune responses of naive and different memory subsets of CD4+ and CD8+ T cells to HHV-6 have not been investigated. We show that HHV-6A induces cell division, as measured by CFSE dye and flow cytometry, predominantly in two populations of effector memory CD4+ and CD8+ T cells (TEM and TEMRA); naïve (TN) and central memory (TCM) CD4+ and CD8+ T cells show almost no cell division. In contrast, HHV-6A induces apoptosis primarily in TN and TCM CD4+ and CD8+ T cells, whereas TEM and TEMRA CD4+ and CD8+ were resistant to HHV-6A-induced apoptosis. HHV-6A-induced apoptosis was associated with activation of caspase-8, caspase-9 and caspase-3, suggesting involvement of death receptor and mitochondrial signaling pathways. In addition, HHV-6A induced secretion of IL-6, TNF-{alpha}, IL-8, and IFN-{gamma} by peripheral blood mononuclear cells; TNF-{alpha}, secretion was observed exclusively from CCR7+ (TN plus TCM ) CD4+ T cells. These data show that HHV-6 differentially influences functions of naïve and different subsets of memory CD4+ and CD8+ T cells, which in part may be due to differential susceptibility to HHV-6A-induced apoptosis.