Differential effect of human herpesvirus 6A on cell division and apoptosis among naive and central and effector memory CD4+ and CD8+ T-cell subsets.
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)); naïve (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 naïve 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.
Gupta
Sudhir
S
Division of Basic and Clinical Immunology, University of California, Irvine, California 92697, USA. sgupta@uci.edu
Agrawal
Sudhanshu
S
Gollapudi
Sastry
S
D017209:Apoptosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D015654:Herpesvirus 6, Human / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology*; D051916:Membrane Cofactor Protein / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
D016207:Cytokines; D051916:Membrane Cofactor Protein; D019253:Proto-Oncogene Proteins c-bcl-2