title: Combined Env- and Gag-specific T cell responses in relation to programmed death-1 receptor and CD4 T cell loss rates in human immunodeficiency virus-1 infection.
abstract: Additional progression markers for human immunodeficiency virus (HIV) infection are warranted. In this study we related antigen-specific responses in CD4(+) and CD8(+) T cells to CD38, reflecting chronic immune activation, and to CD4(+) T cell loss rates. Clones transiently expressing CD107a (CD8(+)) or CD154 (CD4(+)) in response to Gag, Env and Nef overlapping peptide pools were identified, along with their expression of the inhibitory programmed death-1 receptor (PD-1) in fresh peripheral blood mononuclear cells (PBMC) from 31 patients off antiretroviral treatment (ART). HIV-specific CD8(+) T cell responses dominated over CD4(+) T cell responses, and among CD8(+) responses, Gag and Nef responses were higher than Env-responses (P < 0.01). PD-1 on CD8(+) HIV-specific subsets was higher than CMV-specific CD8(+) cells (P < 0.01), whereas PD-1 on HIV-specific CD4(+) cells was similar to PD-1 on CMV-specific CD4(+) cells. Gag and Env CD8(+) responses correlated oppositely to the CD4 loss rate. Env/Gag CD8(+) response ratios, independently of PD-1 levels, correlated more strongly to CD4 change rates (r = -0.50 to -0.77, P < 0.01) than the total number of Gag-specific CD8(+) cells (r = 0.44-0.85, P < or = 0.02). The Env/Gag ratio performed better than CD38 and HIV-RNA in logistic regression analysis predicting CD4 change rate as a measure of progression. In conclusion, HIV-specific CD8(+)CD107a(+) Env/Gag response ratio was a stronger predictor for progression than CD38 and HIV-RNA. The Env/Gag ratio may reflect the balance between possibly beneficial (Gag) and detrimental (Env) CD8(+) T cell responses and should be explored further as a progression marker.
authors.affiliation: Ullevål Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway.
authors.forename: F O
authors.initials: FO
authors.lastname: Pettersen
authors.forename: K
authors.initials: K
authors.lastname: Taskén
authors.forename: D
authors.initials: D
authors.lastname: Kvale
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000175:diagnosis / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016015:Logistic Models; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D010455:Peptides / Q000276:immunology; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D019562:Viral Load; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology*; 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; D008562:Membrane Glycoproteins; C105992:PDCD1 protein, human; D010455:Peptides; D061026:Programmed Cell Death 1 Receptor; D054299:env Gene Products, Human Immunodeficiency Virus; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1