Human CD4+T Cell Response to Human Herpesvirus 6

• DOI: 10.1128/jvi.06573-11
• Publication Date: 2012-02-23T06:30:26Z
• Authors: Maria-D. Nastke; Aniuska Becerra; Liusong Yin; Omar Dominguez-Am...; Laura Gibson; Lawrence J. Stern; J. Mauricio Calvo...
• Keywords: CD4-Positive T-Lymphocytes; 570; Cytotoxic; Herpesvirus 6, Human; T-Lymphocytes; Mononuclear; 610; Epitopes, T-Lymphocyte; Roseolovirus Infections; Cross Reactions; Cell Line; Epitopes; Interferon-gamma; 03 medical and health sciences; 0302 clinical medicine; Virology; Leukocytes; Pathology; Humans; Herpesvirus 6; Viral; Antigens; Antigens, Viral; Immunology and Infectious Disease; HLA-DR1 Antigen; Viral Load; Tissue Donors; 3. Good health; T-Lymphocyte; Haplotypes; Leukocytes, Mononuclear; Cytokines; Protein Multimerization; Peptides; Human; T-Lymphocytes, Cytotoxic

ABSTRACTFollowing 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 easilyin 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.