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In several murine and human chronic infections, the expression of Tim-3 is associated with poor control of viral burden and impaired antiviral immune responses. However, the role of Tim-3+ Tregs during persistent viral infections has not been fully defined. We employed an inducible Treg-specific Tim-3 loss-of-function (Tim-3 Treg knockout) murine model to dissect the role of Tim-3 on Tregs during chronic lymphocytic choriomeningitis virus infection. Tim-3 Treg knockout mice exhibited a decrease in morbidity, a more potent virus-specific T cell response, and a significant decrease in viral burden. These mice also had a reduction in the frequency of PD-1+Tim-3+ and PD-1+Tox+ gp33-specific exhausted CD8+ T cells. Our findings demonstrate that modulation of a single surface protein on Tregs can lead to a reduction in viral burden, limit T cell exhaustion, and enhance gp33-specific T cell response. These studies may help to identify Tim-3\u2013directed therapies for the management of persistent infections and cancer.<\/jats:p>","DOI":"10.4049\/jimmunol.2400119","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T12:59:34Z","timestamp":1727701174000},"page":"1488-1498","source":"Crossref","is-referenced-by-count":11,"title":["Tim-3 Is Required for Regulatory T Cell\u2013Mediated Promotion of T Cell Exhaustion and Viral Persistence during Chronic Lymphocytic Choriomeningitis Virus Infection"],"prefix":"10.1093","volume":"213","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8084-0728","authenticated-orcid":false,"given":"Hector M","family":"Nieves-Rosado","sequence":"first","affiliation":[{"name":"Department of Immunology, University of Pittsburgh , Pittsburgh, PA"},{"name":"Medical Scientist Training Program, University of Pittsburgh and Carnegie Mellon University , Pittsburgh, PA"},{"name":"Graduate Program in Microbiology and Immunology, 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