PMID- 22357271 OWN - NLM STAT- MEDLINE DCOM- 20120618 LR - 20211021 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 86 IP - 9 DP - 2012 May TI - Human CD4+ T cell response to human herpesvirus 6. PG - 4776-92 LID - 10.1128/JVI.06573-11 [doi] AB - 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-gamma) 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. FAU - Nastke, Maria-D AU - Nastke MD AD - Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA. FAU - Becerra, Aniuska AU - Becerra A FAU - Yin, Liusong AU - Yin L FAU - Dominguez-Amorocho, Omar AU - Dominguez-Amorocho O FAU - Gibson, Laura AU - Gibson L FAU - Stern, Lawrence J AU - Stern LJ FAU - Calvo-Calle, J Mauricio AU - Calvo-Calle JM LA - eng GR - P30 DK032520/DK/NIDDK NIH HHS/United States GR - DK32520/DK/NIDDK NIH HHS/United States GR - AI-U19-57319/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20120222 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Antigens, Viral) RN - 0 (Cytokines) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA-DR1 Antigen) RN - 0 (Peptides) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Antigens, Viral/immunology MH - CD4-Positive T-Lymphocytes/*immunology MH - Cell Line MH - Cross Reactions/immunology MH - Cytokines/metabolism MH - Epitopes, T-Lymphocyte/immunology MH - HLA-DR1 Antigen/chemistry/immunology MH - Haplotypes MH - Herpesvirus 6, Human/*immunology MH - Humans MH - Interferon-gamma/metabolism MH - Leukocytes, Mononuclear/immunology MH - Peptides/immunology MH - Protein Multimerization/immunology MH - Roseolovirus Infections/immunology/virology MH - T-Lymphocytes/immunology MH - T-Lymphocytes, Cytotoxic/immunology MH - Tissue Donors MH - Viral Load PMC - PMC3347333 EDAT- 2012/02/24 06:00 MHDA- 2012/06/19 06:00 PMCR- 2012/11/01 CRDT- 2012/02/24 06:00 PHST- 2012/02/24 06:00 [entrez] PHST- 2012/02/24 06:00 [pubmed] PHST- 2012/06/19 06:00 [medline] PHST- 2012/11/01 00:00 [pmc-release] AID - JVI.06573-11 [pii] AID - 06573-11 [pii] AID - 10.1128/JVI.06573-11 [doi] PST - ppublish SO - J Virol. 2012 May;86(9):4776-92. doi: 10.1128/JVI.06573-11. Epub 2012 Feb 22.