Dynamics of SIV-specific CXCR5+CD8 T cells during chronic SIV infection

• Type of Material: Article
• Authors: Geetha H. Mylvaganam, Emory University; Daniel Rios, Emory University; HM Abdelaal, University of Minnesota; Smita Iyer, Emory University; Gregory Tharp, Emory University; Maud Mavigner, Emory University; Sakeenah Hicks, Emory University; Ann Chahroudi, Emory University; Rafi Ahmed, Emory University; Steven Bosinger, Emory University; Ifor Williams, Emory University; Pamela J. Skinner, University of Minnesota; Vijayakumar Velu, Emory University; Rama Amara, Emory University
• Language: English
• Date: 2017-02-21
• Publisher: National Academy of Sciences
• Publication Version: Final Published Version
• Copyright Statement: © 2017 National Academy of Sciences.
• Final Published Version (URL): http://dx.doi.org/10.1073/pnas.1621418114
• Title of Journal or Parent Work: PNAS: Proceedings of the National Academy of Sciences of the United States of America
• Volume: 114
• Issue: 8
• Start Page: 1976
• End Page: 1981
• Grant/Funding Information: This work was supported by National Institutes of Health Grants R36 AI112787, P01 AI88575, and U19 AI109633 (to R.R.A.) and AI096966 (to P.J.S.); Yerkes National Primate Research Center Base Grant P51 RR00165; and Emory Center for AIDS Research Grant P30 AI050409.
• Keywords: Viremia; Lymphoid tissues; HIV; HIV-infection; SIV; Multidisciplinary Sciences; Rhesus macaques; lymphoid follicles; Science & Technology; Expression; CXCR5+CD8+T cells; Viral infection; Human immunodeficiency virus (HIV); Replication; follicular CD8 T cells; Follicular helper; Science & Technology - Other Topics; Follicles
• Research Categories: Health Sciences, Pathology; Health Sciences, Immunology; Biology, Microbiology

Abstract

A significant challenge to HIV eradication is the elimination of viral reservoirs in germinal center (GC) T follicular helper (Tfh) cells. However, GCs are considered to be immune privileged for antiviral CD8 T cells. Here, we show a population of simian immunodeficiency virus (SIV)-specific CD8 T cells express CXCR5 (C-X-C chemokine receptor type 5, a chemokine receptor required for homing to GCs) and expand in lymph nodes (LNs) following pathogenic SIV infection in a cohort of vaccinated macaques. This expansion was greater in animals that exhibited superior control of SIV. The CXCR5+ SIV-specific CD8 T cells demonstrated enhanced polyfunctionality, restricted expansion of antigen-pulsed Tfh cells in vitro, and possessed a unique gene expression pattern related to Tfh and Th2 cells. The increase in CXCR5+ CD8 T cells was associated with the presence of higher frequencies of SIV-specific CD8 T cells in the GC. Following TCR-driven stimulation in vitro, CXCR5+ but not CXCR5- CD8 T cells generated both CXCR5+ as well as CXCR5- cells. However, the addition of TGF-β to CXCR5- CD8 T cells induced a population of CXCR5+ CD8 T cells, suggesting that this cytokine may be important in modulating these CXCR5+ CD8 T cells in vivo. Thus, CXCR5+ CD8 T cells represent a unique subset of antiviral CD8 T cells that expand in LNs during chronic SIV infection and may play a significant role in the control of pathogenic SIV infection.