Phenotypic and functional alterations of dendritic cells induced by human herpesvirus 6 infection.
Human herpesvirus 6 (HHV-6) has a tropism for T lymphocytes and monocytes/macrophages, suggesting that HHV-6 infection affects the immunosurveillance system. In the present study, we investigated the HHV-6-induced phenotypic and functional alterations of dendritic cells (DCs), which are professional antigen-presenting cells. HHV-6 infection of monocyte-derived immature DCs appeared to induce the up-regulation of CD80, CD83, CD86, and HLA class I and class II molecules, suggesting that HHV-6 infection induces the maturation of DCs. In addition, the antigen capture capacity of DCs was found to decrease following infection with HHV-6. In contrast to up-regulation of mature-DC-associated surface molecules on HHV-6-infected DCs, their capacity for presentation of alloantigens and exogenous virus antigens to T lymphocytes decreased significantly from that of uninfected DCs. In contrast, there appeared to be no reduction in the capacity for presentation of an HLA class II-binding peptide to the peptide-specific CD4(+) T lymphocytes. These data indicate that HHV-6 infection induces phenotypic alterations and impairs the antigen presentation capacity of DCs. The present data also suggest that the dysfunction of HHV-6-infected DCs is attributable mainly to impairment of the antigen capture and intracellular antigen-processing pathways.
Kakimoto
Miki
M
First Department of Internal Medicine, Ehime University School of Medicine, Shigenobu, Ehime 791-0295, Japan.
Hasegawa
Atsuhiko
A
Fujita
Shigeru
S
Yasukawa
Masaki
M
D015703:Antigens, CD / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D004705:Endocytosis / Q000276:immunology; D005434:Flow Cytometry / Q000379:methods; D015654:Herpesvirus 6, Human / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D016130:Immunophenotyping; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014779:Virus Replication; D000097802:CD83 Antigen
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D000097802:CD83 Antigen; C497964:CD86 protein, human