Human CD4+ T cell response to human herpesvirus 6
Department of Pathology; Department of Pediatrics; Department of Biochemistry and Molecular Pharmacology
Medical Subject Headings
Antigens, Viral; CD4-Positive T-Lymphocytes; Cell Line; Cross Reactions; Cytokines; Epitopes, T-Lymphocyte; HLA-DR1 Antigen; Haplotypes; Herpesvirus 6, Human; Humans; Interferon-gamma; Leukocytes, Mononuclear; Peptides; Protein Multimerization; Roseolovirus Infections; T-Lymphocytes; T-Lymphocytes, Cytotoxic; Tissue Donors; Viral Load
Immunology and Infectious Disease | Pathology | Virology
Following primary infection, human herpesvirus 6 (HHV-6) establishes a persistent infection for life. HHV-6 reactivation has been associated with transplant rejection, delayed engraftment, encephalitis, muscular dystrophy, and drug-induced hypersensitivity syndrome. The poor understanding of the targets and outcome of the cellular immune response to HHV-6 makes it difficult to outline the role of HHV-6 in human disease. To fill in this gap, we characterized CD4 T cell responses to HHV-6 using peripheral blood mononuclear cell (PBMC) and T cell lines generated from healthy donors. CD4(+) T cells responding to HHV-6 in peripheral blood were observed at frequencies below 0.1% of total T cells but could be expanded easily in vitro. Analysis of cytokines in supernatants of PBMC and T cell cultures challenged with HHV-6 preparations indicated that gamma interferon (IFN-γ) and interleukin-10 (IL-10) were appropriate markers of the HHV-6 cellular response. Eleven CD4(+) T cell epitopes, all but one derived from abundant virion components, were identified. The response was highly cross-reactive between HHV-6A and HHV-6B variants. Seven of the CD4(+) T cell epitopes do not share significant homologies with other known human pathogens, including the closely related human viruses human herpesvirus 7 (HHV-7) and human cytomegalovirus (HCMV). Major histocompatibility complex (MHC) tetramers generated with these epitopes were able to detect HHV-6-specific T cell populations. These findings provide a window into the immune response to HHV-6 and provide a basis for tracking HHV-6 cellular immune responses.
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Citation: J Virol. 2012 May;86(9):4776-92. Epub 2012 Feb 22. doi: 10.1128/JVI.06573-11