Immune targeting of PD-1(hi) expressing cells during and after antiretroviral therapy in SIV-infected rhesus macaques

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-infect...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2013-12, Vol.447 (1-2), p.274-284
Main Authors: Vargas-Inchaustegui, Diego A, Xiao, Peng, Hogg, Alison E, Demberg, Thorsten, McKinnon, Katherine, Venzon, David, Brocca-Cofano, Egidio, Dipasquale, Janet, Lee, Eun M, Hudacik, Lauren, Pal, Ranajit, Sui, Yongjun, Berzofsky, Jay A, Liu, Linda, Langermann, Solomon, Robert-Guroff, Marjorie
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Animals
Anti-Retroviral Agents - therapeutic use
ANTIGENS
Antiretroviral Therapy, Highly Active - methods
CELL PROLIFERATION
COMPARATIVE EVALUATIONS
DISTRIBUTION
Immunologic Factors - therapeutic use
Immunotherapy - methods
LYMPH NODES
Macaca mulatta
PHENOTYPE
Programmed Cell Death 1 Receptor - biosynthesis
PROTEINS
Simian Acquired Immunodeficiency Syndrome - therapy
T-Lymphocytes - immunology
THERAPY
Viral Load
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Summary: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.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2013.09.015