Immune targeting of PD-1{sup 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{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 Tregmore »
- Authors:
-
- Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)
- Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)
- Advanced Bioscience Laboratories Inc., Rockville, MD 20850 (United States)
- Amplimmune Inc., Gaithersburg, MD 20878 (United States)
- Publication Date:
- OSTI Identifier:
- 22436667
- Resource Type:
- Journal Article
- Journal Name:
- Virology
- Additional Journal Information:
- Journal Volume: 447; Journal 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); Journal ID: ISSN 0042-6822
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; ANTIGENS; CELL PROLIFERATION; COMPARATIVE EVALUATIONS; DISTRIBUTION; LYMPH NODES; PHENOTYPE; PROTEINS; THERAPY
Citation Formats
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, and Robert-Guroff, Marjorie. Immune targeting of PD-1{sup hi} expressing cells during and after antiretroviral therapy in SIV-infected rhesus macaques. United States: N. p., 2013.
Web. doi:10.1016/J.VIROL.2013.09.015.
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. Immune targeting of PD-1{sup hi} expressing cells during and after antiretroviral therapy in SIV-infected rhesus macaques. United States. https://doi.org/10.1016/J.VIROL.2013.09.015
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, and Robert-Guroff, Marjorie. 2013.
"Immune targeting of PD-1{sup hi} expressing cells during and after antiretroviral therapy in SIV-infected rhesus macaques". United States. https://doi.org/10.1016/J.VIROL.2013.09.015.
@article{osti_22436667,
title = {Immune targeting of PD-1{sup hi} expressing cells during and after antiretroviral therapy in SIV-infected rhesus macaques},
author = {Vargas-Inchaustegui, Diego A. and Xiao, Peng and Hogg, Alison E. and Demberg, Thorsten and McKinnon, Katherine and Venzon, David and Brocca-Cofano, Egidio and DiPasquale, Janet and Lee, Eun M. and Hudacik, Lauren and Pal, Ranajit and Sui, Yongjun and Berzofsky, Jay A. and Liu, Linda and Langermann, Solomon and Robert-Guroff, Marjorie},
abstractNote = {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.},
doi = {10.1016/J.VIROL.2013.09.015},
url = {https://www.osti.gov/biblio/22436667},
journal = {Virology},
issn = {0042-6822},
number = 1-2,
volume = 447,
place = {United States},
year = {Sun Dec 15 00:00:00 EST 2013},
month = {Sun Dec 15 00:00:00 EST 2013}
}