Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6140527 | Virology | 2013 | 11 Pages |
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-1hi expressing T cells and Tregs in PBMCs, and PD-1hi 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-1hi cells during and post-ART helps maintain lower viremia, keeps a favorable T cell/Treg repertoire and modulates antigen-specific responses.
Keywords
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Authors
Diego A. Vargas-Inchaustegui, Peng Xiao, Alison E. Hogg, Thorsten Demberg, Katherine McKinnon, David Venzon, Egidio Brocca-Cofano, Janet DiPasquale, Eun M. Lee, Lauren Hudacik, Ranajit Pal, Yongjun Sui, Jay A. Berzofsky, Linda Liu, Solomon Langermann,