Immune targeting of PD-1{sup hi} expressing cells during and after antiretroviral therapy in SIV-infected rhesus macaques

Journal Article · Sun Dec 15 00:00:00 EST 2013 · Virology

DOI:https://doi.org/10.1016/J.VIROL.2013.09.015· OSTI ID:22436667

Vargas-Inchaustegui, Diego A.; Xiao, Peng; Hogg, Alison E.; Demberg, Thorsten; McKinnon, Katherine ^[1]; Venzon, David ^[2]; Brocca-Cofano, Egidio; DiPasquale, Janet ^[1]; Lee, Eun M.; Hudacik, Lauren; Pal, Ranajit ^[3]; Sui, Yongjun; Berzofsky, Jay A. ^[1]; Liu, Linda; Langermann, Solomon ^[4]; Robert-Guroff, Marjorie ^[1]

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1. Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)
2. Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)
3. Advanced Bioscience Laboratories Inc., Rockville, MD 20850 (United States)
4. Amplimmune Inc., Gaithersburg, MD 20878 (United States)

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{sup hi} expressing T cells and Tregs in PBMCs, and PD-1{sup hi} Tregs in lymph nodes. It transiently decreased expression of Ki67 and α{sub 4}β{sub 7} in PBMC CD4{sup +} and CD8{sup +} Tregs for up to 8 weeks post-ART and maintained Ag-specific T-cell responses at low levels. Continued immune modulation targeting PD-1{sup hi} cells during and post-ART helps maintain lower viremia, keeps a favorable T cell/Treg repertoire and modulates antigen-specific responses. - Highlights: • B7-DC-Ig modulates PD-1{sup hi} cells in SIV-infected rhesus macaques during and post-ART. • Continued PD-1 modulation post-ART maintains PD-1{sup hi} cells at low levels. • Continued PD-1 modulation post-ART maintains a favorable T cell and Treg repertoire.

• OSTI ID: 22436667
• Journal Information: Virology, Vol. 447, Issue 1-2; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANTIGENS
CELL PROLIFERATION
COMPARATIVE EVALUATIONS
DISTRIBUTION
LYMPH NODES
PHENOTYPE
PROTEINS
THERAPY