Relationships between IL-17+ Subsets, Tregs and pDCs That Distinguish among SIV Infected Elite Controllers, Low, Medium and High Viral Load Rhesus Macaques

• Type of Material: Article
• Authors: Ladawan Khowawisetsut, Emory University; Kovit Pattanapanyasat, Mahidol University; Nattawat Onlamoon, Mahidol University; Ann E. Mayne, Emory University; Dawn Little, Emory University; Francois Villinger, Emory University; Aftab A Ansari, Emory University
• Language: English
• Date: 2013-04-19
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2013 Khowawisetsut et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0061264
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 8
• Issue: 4
• Start Page: 1
• End Page: 19
• Grant/Funding Information: Professor Kovit Pattanapanyasat is the recipient of the TRF, Senior Research Scholar Award. Supported by a grant from the National Institutes of Health-National Institute of Allergy and Infectious Diseases RO1 AI078773 and OD 51POD1113 to the Yerkes National Primate Research Center.; Ms. Ladawan Khowawisetsut was financially supported by a fellowship from the Thailand Research Fund (TRF)- The Royal Golden Jubilee Ph.D. Program (PHD/0198/2550), and the studies reported above are in partial fulfillment of her doctoral thesis.
• Research Categories: Health Sciences, Pathology; Health Sciences, Immunology

Abstract

Comprehensive studies of the frequencies and absolute numbers of the various cell lineages that synthesize IL-17 in the blood and corresponding gastrointestinal (GI) tissues, their correlation with CD4+ Tregs, CD8+ Tregs, total and IFN-α synthesizing plasmacytoid dendritic cells (pDC) relative to plasma viral load in SIV infection has been lacking. The unique availability of SIV infected rhesus macaques (RM) classified as Elite Controllers (EC), and those with Low, Intermediate and High Viral Loads (HVL) provided a unique opportunity to address this issue. Results of these studies showed that EC demonstrated a remarkable ability to reverse changes that are induced acutely by SIV in the various cell lineages. Highlights of the differences between EC and HVL RM within Gastro-intestinal tissues (GIT) was the maintenance and/or increases in the levels of IL-17 synthesizing CD4, CD8, and NK cells and pDCs associated with slight decreases in the levels of CD4+ Tregs and IFN-α synthesizing pDCs in EC as compared with decreases in the levels of IL-17 synthesizing CD4, CD8 and NK cells associated with increases in pDCs and IFN-α synthesizing pDCs in HVL monkeys. A previously underappreciated role for CD8+ Tregs was also noted with a moderate increase in ECs but further increases of CD8+ Tregs with increasing VL in viremic monkeys. Positive correlations between plasma VL and decreases in the levels of Th17, Tc17, NK-17, CD4+ Tregs and increases in the levels of CD8+ Tregs, total and IFN-α synthesizing pDCs were also noted. This study also identified 2 additional IL-17+ subsets in GIT as CD3−/CD8+/NKG2a− and CD3+/CD8+/NKG2a+ subsets. Studies also suggest a limited role for IFN-α synthesizing pDCs in chronic immune activation despite persistent up-regulation of ISGs. Finally, elevated persistent innate immune responses appear associated with poor prognosis. These findings provide an initial foundation for markers important to follow for vaccine design.