title: Immune targeting of PD-1(hi) expressing cells during and after antiretroviral therapy in SIV-infected rhesus macaques.
abstract: High-level T cell expression of PD-1 during SIV infection is correlated with impaired proliferation and function. We evaluated the phenotype and distribution of T cells and Tregs during antiretroviral therapy plus PD-1 modulation (using a B7-DC-Ig fusion protein) and post-ART. Chronically SIV-infected rhesus macaques received: 11 weeks of ART (Group A); 11 weeks of ART plus B7-DC-Ig (Group B); 11 weeks of ART plus B7-DC-Ig, then 12 weeks of B7-DC-Ig alone (Group C). Continuous B7-DC-Ig treatment (Group C) decreased rebound viremia post-ART compared to pre-ART levels, associated with decreased PD-1(hi) expressing T cells and Tregs in PBMCs, and PD-1(hi) Tregs in lymph nodes. It transiently decreased expression of Ki67 and α4β7 in PBMC CD4(+) and CD8(+) Tregs for up to 8 weeks post-ART and maintained Ag-specific T-cell responses at low levels. Continued immune modulation targeting PD-1(hi) cells during and post-ART helps maintain lower viremia, keeps a favorable T cell/Treg repertoire and modulates antigen-specific responses.
authors.affiliation: Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Diego A
authors.initials: DA
authors.lastname: Vargas-Inchaustegui
authors.forename: Peng
authors.initials: P
authors.lastname: Xiao
authors.forename: Alison E
authors.initials: AE
authors.lastname: Hogg
authors.forename: Thorsten
authors.initials: T
authors.lastname: Demberg
authors.forename: Katherine
authors.initials: K
authors.lastname: McKinnon
authors.forename: David
authors.initials: D
authors.lastname: Venzon
authors.forename: Egidio
authors.initials: E
authors.lastname: Brocca-Cofano
authors.forename: Janet
authors.initials: J
authors.lastname: Dipasquale
authors.forename: Eun M
authors.initials: EM
authors.lastname: Lee
authors.forename: Lauren
authors.initials: L
authors.lastname: Hudacik
authors.forename: Ranajit
authors.initials: R
authors.lastname: Pal
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Sui
authors.forename: Jay A
authors.initials: JA
authors.lastname: Berzofsky
authors.forename: Linda
authors.initials: L
authors.lastname: Liu
authors.forename: Solomon
authors.initials: S
authors.lastname: Langermann
authors.forename: Marjorie
authors.initials: M
authors.lastname: Robert-Guroff
mesh_terms: D000818:Animals; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D007155:Immunologic Factors / Q000627:therapeutic use*; D007167:Immunotherapy / Q000379:methods*; D008253:Macaca mulatta; D061026:Programmed Cell Death 1 Receptor / Q000096:biosynthesis*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D007155:Immunologic Factors; D061026:Programmed Cell Death 1 Receptor
keywords: ART; Immunomodulation; PD-1; Treg; Viremia