| First Author | Garidou L | Year | 2012 |
| Journal | J Virol | Volume | 86 |
| Issue | 13 | Pages | 7060-71 |
| PubMed ID | 22553324 | Mgi Jnum | J:186188 |
| Mgi Id | MGI:5431171 | Doi | 10.1128/JVI.00164-12 |
| Citation | Garidou L, et al. (2012) Therapeutic blockade of transforming growth factor beta fails to promote clearance of a persistent viral infection. J Virol 86(13):7060-71 |
| abstractText | Persistent viral infections often overburden the immune system and are a major cause of disease in humans. During many persistent infections, antiviral T cells are maintained in a state of immune exhaustion characterized by diminished effector and helper functions. 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-beta) 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-beta 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-beta is not an efficacious means to promote clearance of a persistent viral infection. |
