PMID- 19297473 OWN - NLM STAT- MEDLINE DCOM- 20090529 LR - 20211020 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 83 IP - 11 DP - 2009 Jun TI - Differential effect of human herpesvirus 6A on cell division and apoptosis among naive and central and effector memory CD4+ and CD8+ T-cell subsets. PG - 5442-50 LID - 10.1128/JVI.00106-09 [doi] AB - The immune responses of naive and different memory subsets of CD4(+) and CD8(+) T cells to human herpesvirus 6 (HHV-6) have not been previously investigated. We show that HHV-6A induces cell division, as measured by 5,6-carboxyfluorescein succinimidyl ester dye and flow cytometry, predominantly in two populations of effector memory CD4(+) and CD8(+) T cells (T(EM) and T(EMRA)); naive (T(N)) and central memory (T(CM)) CD4(+) and CD8(+) T cells showed almost no cell division. In contrast, HHV-6A induced apoptosis primarily in T(N) and T(CM) CD4(+) and CD8(+) T cells, whereas T(EM) and T(EMRA) CD4(+) and CD8(+) T cells were resistant to HHV-6A-induced apoptosis. HHV-6A-induced apoptosis was associated with activation of caspase-8, caspase-9, and caspase-3, suggesting the involvement of death receptor and mitochondrial signaling pathways. In addition, HHV-6A induced secretion of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), IL-8, and gamma interferon by peripheral blood mononuclear cells; TNF-alpha secretion was observed exclusively from CCR7(+) (T(N) plus T(CM)) CD4(+) T cells. These data show that HHV-6 differentially influences the functions of naive T cells and different subsets of memory CD4(+) and CD8(+) T cells, which in part may be due to differential susceptibility to HHV-6A-induced apoptosis. FAU - Gupta, Sudhir AU - Gupta S AD - Division of Basic and Clinical Immunology, University of California, Irvine, California 92697, USA. sgupta@uci.edu FAU - Agrawal, Sudhanshu AU - Agrawal S FAU - Gollapudi, Sastry AU - Gollapudi S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090318 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Cytokines) RN - 0 (Membrane Cofactor Protein) RN - 0 (Proto-Oncogene Proteins c-bcl-2) SB - IM MH - Apoptosis/*immunology MH - CD4-Positive T-Lymphocytes/cytology/*immunology/metabolism MH - CD8-Positive T-Lymphocytes/cytology/*immunology/metabolism MH - Cell Division/immunology MH - Cells, Cultured MH - Cytokines/biosynthesis/immunology MH - Herpesvirus 6, Human/*immunology MH - Humans MH - Immunity, Innate/*immunology MH - Immunologic Memory/*immunology MH - Membrane Cofactor Protein/immunology MH - Proto-Oncogene Proteins c-bcl-2/metabolism MH - T-Lymphocyte Subsets/cytology/*immunology MH - Up-Regulation/immunology PMC - PMC2681935 EDAT- 2009/03/20 09:00 MHDA- 2009/05/30 09:00 PMCR- 2009/12/01 CRDT- 2009/03/20 09:00 PHST- 2009/03/20 09:00 [entrez] PHST- 2009/03/20 09:00 [pubmed] PHST- 2009/05/30 09:00 [medline] PHST- 2009/12/01 00:00 [pmc-release] AID - JVI.00106-09 [pii] AID - 0106-09 [pii] AID - 10.1128/JVI.00106-09 [doi] PST - ppublish SO - J Virol. 2009 Jun;83(11):5442-50. doi: 10.1128/JVI.00106-09. Epub 2009 Mar 18.