title: Presence of suppressor HIV-specific CD8+ T cells is associated with increased PD-1 expression on effector CD8+ T cells.
abstract: Mechanisms leading to the observed immune dysregulation in HIV-1 infection are not well understood. HIV-specific IL-10-positive CD8(+) T cells are increased in advanced HIV disease. We have previously reported that Gag-specific IL-10-positive CD8(+) T cells suppressed cytolysis. In this study we describe the suppressive effect of Nef-specific IL-10-positive CD8(+) T cells. Interestingly, simultaneous removal of both Gag- and Nef-specific IL-10-positive CD8(+) T cells led to higher HIV-specific cytolysis compared with the removal of Nef-specific IL-10-positive CD8(+) T cells alone. We also examined the level of programmed cell death-1 (PD-1) as a measure of immune dysfunction in association with IL-10-positive suppressor CD8(+) T cells. The level of PD-1 expression on CD107-positive effector CD8(+) T cells was significantly increased when IL-10-positive suppressor CD8(+) T cells were present (p < 0.05). Our results suggest that IL-10-positive suppressor CD8(+) T cells contribute to the immune dysfunction observed in advanced HIV infection and that the concomitant presence of multiple IL-10-positive CD8(+) T cell populations may have an additive suppressive effect.
authors.affiliation: California Department of Public Health, Richmond, CA 94804, USA. melrefae@cdph.ca.gov
authors.forename: Mohamed
authors.initials: M
authors.lastname: Elrefaei
authors.forename: Chris A R
authors.initials: CA
authors.lastname: Baker
authors.forename: Norman G
authors.initials: NG
authors.lastname: Jones
authors.forename: David R
authors.initials: DR
authors.lastname: Bangsberg
authors.forename: Huyen
authors.initials: H
authors.lastname: Cao
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D016212:Transforming Growth Factor beta; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus; D016753:Interleukin-10