title: Regulatory T Cell Effect on CD8+T Cell Responses to Human Herpesvirus 8 Infection and Development of Kaposi's Sarcoma.
abstract: We assessed CD8+T cell reactivity to human herpesvirus 8 (HHV-8; Kaposi's sarcoma [KS]-associated herpesvirus) and the role of CD4+CD25hiFoxP3+regulatory T cells (Treg) in HHV-8- and HIV-coinfected participants of the Multicenter AIDS Cohort Study who did or did not develop KS. There were similarly low CD8+T cell interferon-γ responses to MHC class I-restricted epitopes of HHV-8 lytic and latent proteins over 5.7 years before KS in participants who developed KS compared to those who did not. T cell reactivity to HHV-8 antigens was low relative to responses to a combination of cytomegalovirus, Epstein-Barr virus and influenza A virus (CEF) peptide epitopes, and dominant HIV peptide epitopes. There was no change in %Treg in the HHV-8- and HIV-coinfected participants who did not develop KS, whereas there was a significant increase in %Treg in HHV-8- and HIV-coinfected participants who developed KS beginning 1.8 years before development of KS. Removal of Treg enhanced HHV-8-specific T cell responses in HHV-8- and HIV-coinfected participants who did or did not develop KS, with a similar pattern observed in response to CEF and HIV peptides. Thus, long-term, low levels of anti-HHV-8 CD8+T cell reactivity were present in both HHV-8- and HIV-coinfected men who did and did not develop KS. This was related to moderately enhanced Treg function.
authors.affiliation: 1 Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Lepone
authors.affiliation: 1 Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Rappocciolo
authors.affiliation: 1 Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Piazza
authors.affiliation: 1 Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Campbell
authors.affiliation: 1 Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh , Pittsburgh, Pennsylvania.|2 Department of Pathology, School of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Jenkins
authors.affiliation: 1 Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh , Pittsburgh, Pennsylvania.|2 Department of Pathology, School of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Rinaldo
mesh_terms: D000328:Adult; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006566:Herpesviridae Infections / Q000150:complications* / Q000821:virology*; D019288:Herpesvirus 8, Human / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012514:Sarcoma, Kaposi / Q000473:pathology* / Q000821:virology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult
chemical_list: D000956:Antigens, Viral; D007371:Interferon-gamma
keywords: HIV/AIDS pathogenesis; T cell immunity; T cells; immune response