Accumulation of follicular CD8(+) T cells in pathogenic SIV infection

• Type of Material: Article
• Authors: Sara Ferrando-Martinez, National Institutes of Health; Eirini Moysi, National Institutes of Health; Amarendra Pegu, National Institutes of Health; Sarah Andrews, National Institutes of Health; Krystelle Nganou Makamdop, National Institutes of Health; David Ambrozak, National Institutes of Health; Adrian B. McDermott, National Institutes of Health; David Palesch, Emory University; Mirko Paiardini, Emory University; George N. Pavlakis, National Cancer Institute; Jason M. Brenchley, National Institutes of Health; Daniel Douek, National Institutes of Health; John R. Mascola, National Institutes of Health; Constantinos Petrovas, National Institutes of Health; Richard A. Koup, National Institutes of Health
• Language: English
• Date: 2018-05-01
• Publisher: American Society for Clinical Investigation
• Publication Version: Final Published Version
• Copyright Statement: © 2018, American Society for Clinical Investigation
• Final Published Version (URL): http://dx.doi.org/10.1172/JCI96207
• Title of Journal or Parent Work: Journal of Clinical Investigation
• ISSN: 0021-9738
• Volume: 128
• Issue: 5
• Start Page: 2089
• End Page: 2103
• Grant/Funding Information: This project was supported in part by a Yerkes National Primate Research Center Base Grant (ORIP/OD P51OD011132).; This research was supported by the Intramural Research Program of the VRC, NIAID and NCI, NIH, and a Collaboration for AIDS Vaccine Discovery (CAVD) grant (OP1032325) from the Bill and Melinda Gates Foundation (to RAK).
• Keywords: Science & Technology; DENDRITIC CELLS; Life Sciences & Biomedicine; IMMUNE ACTIVATION; Research & Experimental Medicine; IN-VIVO; Medicine, Research & Experimental; IMMUNODEFICIENCY-VIRUS-INFECTION; AFRICAN-GREEN MONKEYS; SECONDARY LYMPHOID-TISSUES; EFFECTOR; REPLICATION; RHESUS MACAQUES; HIV-INFECTION
• Research Categories: Health Sciences, Pathology; Biology, Virology; Health Sciences, Immunology

Abstract

LN follicles constitute major reservoir sites for HIV/SIV persistence. Cure strategies could benefit from the characterization of CD8+ T cells able to access and eliminate HIV-infected cells from these areas. In this study, we provide a comprehensive analysis of the phenotype, frequency, localization, and functionality of follicular CD8+ T cells (fCD8+) in SIV-infected nonhuman primates. Although disorganization of follicles was a major factor, significant accumulation of fCD8+ cells during chronic SIV infection was also observed in intact follicles, but only in pathogenic SIV infection. In line with this, tissue inflammatory mediators were strongly associated with the accumulation of fCD8+cells, pointing to tissue inflammation as a major factor in this process. These fCD8+ cells have cytolytic potential and can be redirected to target and kill HIV-infected cells using bispecific antibodies. Altogether, our data support the use of SIV infection to better understand the dynamics of fCD8+ cells and to develop bispecific antibodies as a strategy for virus eradication.