Human herpesvirus 6 infection of CD4+ T-cell subsets.
The immune system includes CD4+ regulatory T (T reg) cells that play a role in self-tolerance and demonstrate functional variations that govern immune responses. HHV-6 is an important immunosuppressive virus that completely replicates in vivo and in vitro in only CD4+ T cells. However, there have been no reports of the specific T-cell subpopulation that permits the replication of this virus. Here, we evaluated the infectivity of HHV-6 to specific T-cell populations such as CD4+CD25 high, which includes the majority of T reg cells, and CD4+CD25(-). These cells were isolated from peripheral blood and then expanded. The expanded cell fractions were then infected with the HHV-6 variant B strain, and the spreads of infected cells were evaluated by immunofluorescence. Viral growth was also quantified by real-time PCR. The effects of virus infection on cytokine production from these T-cell subsets were examined using ELISA. Our results revealed that both these fractions permitted complete HHV-6 replication. Virus infection enhanced the production of both Th1- and Th2-type cytokines from CD4+CD25(-) T cells; however, only Th2-type cytokine release was augmented from viral-infected CD4+CD25 high T cells. Further, while virusinfected CD4+CD25 high T cells shift their antiviral immunity toward Th2 dominance by producing IL-10, the role of virus-infected CD4+CD25(-) T cells remains obscure.
Otani
Naruhito
N
Department of Microbiology, Hyogo College of Medicine, Niishinomiya, Hyogo 663-8501, Japan.
Okuno
Toshiomi
T
D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D015654:Herpesvirus 6, Human / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D008213:Lymphocyte Activation; D050378:T-Lymphocytes, Regulatory / Q000821:virology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014779:Virus Replication
D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit; D016753:Interleukin-10