CD4⁺CD25⁺ Regulatory T Cells Control the Severity of Viral Immunoinflammatory Lesions

CD4⁺CD25⁺ regulatory T cells (T_reg) can inhibit a variety of autoimmune and inflammatory diseases, but their involvement in regulating virus-induced immunopathology is not known. We have evaluated the role of T_reg in viral immunopathological lesion stromal keratitis. This frequent cause of human blindness results from a T cell-mediated immunoinflammatory response to HSV in the corneal stroma. The results show that lesions were significantly more severe if mice were depleted of T_reg before infection. The T_reg was also shown to modulate lesion expression induced by adoptive transfer of pathogenic CD4 ⁺ T cells in infected SCID recipients. The mechanism of T _reg control of stromal keratitis involved suppressed antiviral immunity and impaired expression of the molecule required for T cell migration to lesion sites. Interestingly, T_reg isolated from ocular lesions in nondepleted mice showed in vitro inhibitory effects involving IL-10, but were not very effective in established lesions. Our results decipher the in vivo role of T_reg in a virus-induced immunopathology and imply that manipulation of regulatory cell function represents a useful approach to control viral-induced immunoinflammatory disease.