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SIV-specific CD8+ T cells are clonotypically distinct across lymphoid and mucosal tissues

Starke, Carly E., Vinton, Carol L., Ladell, Kristin ORCID:, McLaren, James E. ORCID:, Ortiz, Alexandra M., Mudd, Joseph C., Flynn, Jacob K., Lai, Stephen H., Wu, Fan, Hirsch, Vanessa M., Darko, Samuel, Douek, Daniel C., Price, David A. ORCID: and Brenchley, Jason M. 2020. SIV-specific CD8+ T cells are clonotypically distinct across lymphoid and mucosal tissues. Journal of Clinical Investigation 130 (2) , pp. 789-798. 10.1172/JCI129161

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CD8+ T cell responses are necessary for immune control of simian immunodeficiency virus (SIV). However, the key parameters that dictate antiviral potency remain elusive, conceivably because most studies to date have been restricted to analyses of circulating CD8+ T cells. We conducted a detailed clonotypic, functional, and phenotypic survey of SIV-specific CD8+ T cells across multiple anatomical sites in chronically infected rhesus macaques with high (>10,000 copies/mL plasma) or low burdens of viral RNA (<10,000 copies/mL plasma). No significant differences in response magnitude were identified across anatomical compartments. Rhesus macaques with low viral loads (VLs) harbored higher frequencies of polyfunctional CXCR5+ SIV-specific CD8+ T cells in various lymphoid tissues and higher proportions of unique Gag-specific CD8+ T cell clonotypes in the mesenteric lymph nodes relative to rhesus macaques with high VLs. In addition, public Gag-specific CD8+ T cell clonotypes were more commonly shared across distinct anatomical sites than the corresponding private clonotypes, which tended to form tissue-specific repertoires, especially in the peripheral blood and the gastrointestinal tract. Collectively, these data suggest that functionality and tissue localization are important determinants of CD8+ T cell–mediated efficacy against SIV.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Publisher: American Society for Clinical Investigation
ISSN: 0021-9738
Date of First Compliant Deposit: 5 March 2020
Date of Acceptance: 22 October 2019
Last Modified: 05 May 2023 00:45

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