title: Human CD4+ T cell response to human herpesvirus 6.
abstract: 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.
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Maria-D
authors.initials: MD
authors.lastname: Nastke
authors.forename: Aniuska
authors.initials: A
authors.lastname: Becerra
authors.forename: Liusong
authors.initials: L
authors.lastname: Yin
authors.forename: Omar
authors.initials: O
authors.lastname: Dominguez-Amorocho
authors.forename: Laura
authors.initials: L
authors.lastname: Gibson
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Stern
authors.forename: J Mauricio
authors.initials: JM
authors.lastname: Calvo-Calle
mesh_terms: D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003429:Cross Reactions / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015798:HLA-DR1 Antigen / Q000737:chemistry / Q000276:immunology; D006239:Haplotypes; D015654:Herpesvirus 6, Human / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D010455:Peptides / Q000276:immunology; D055503:Protein Multimerization / Q000276:immunology; D019349:Roseolovirus Infections / Q000276:immunology / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014019:Tissue Donors; D019562:Viral Load
chemical_list: D000956:Antigens, Viral; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D015798:HLA-DR1 Antigen; D010455:Peptides; D007371:Interferon-gamma