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In mammalian systems, an extensive immune regulatory network exists to limit unwanted, potentially fatal immunopathology by inducing T cell exhaustion. However, this regulatory network at times overprotects the host and fosters viral persistence by severely dampening adaptive immune responsiveness. Importantly, recent studies have shown that T cell exhaustion is mediated in part by host immunoregulatory pathways (e.g., programmed death 1 [PD-1], interleukin 10 [IL-10]) and that therapeutic blockade of these pathways either before or during persistent infection can promote viral clearance. Transforming growth factor beta (TGF-\u03b2) is another immunosuppressive cytokine known to impede both self- and tumor-specific T cells, but its role in regulating antiviral immunity is not entirely understood. In this study, we inhibited TGF-\u03b2 with three potent antagonists to determine whether neutralization of this regulatory molecule is a viable approach to control a persistent viral infection. Our results revealed that these inhibitors modestly elevate the number of antiviral T cells following infection with a persistent variant of lymphocytic choriomeningitis virus (LCMV) but have no impact on viral clearance. These data suggest that therapeutic neutralization of TGF-\u03b2 is not an efficacious means to promote clearance of a persistent viral infection.<\/jats:p>","DOI":"10.1128\/jvi.00164-12","type":"journal-article","created":{"date-parts":[[2012,5,2]],"date-time":"2012-05-02T21:53:16Z","timestamp":1335995596000},"page":"7060-7071","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":42,"title":["Therapeutic Blockade of Transforming Growth Factor Beta Fails To Promote Clearance of a Persistent Viral Infection"],"prefix":"10.1128","volume":"86","author":[{"given":"Lucile","family":"Garidou","sequence":"first","affiliation":[{"name":"INSERM, U1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases (I2MC), Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Heydari","sequence":"additional","affiliation":[{"name":"National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selamawit","family":"Gossa","sequence":"additional","affiliation":[{"name":"National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorian B.","family":"McGavern","sequence":"additional","affiliation":[{"name":"National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.160.2.521"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.62.9.3301-3308.1988"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04444"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002549"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1999.0074"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-4079"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1011998107"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1679"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2007.02.006"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02844-06"},{"key":"e_1_3_2_12_2","unstructured":"BorrowP OldstoneMBA. 1997. 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