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.
Suvas
Susmit
S
Department of Microbiology, University of Tennessee, Knoxville, TN 37996, USA.
Azkur
Ahmet Kursat
AK
Kim
Bum Seok
BS
Kumaraguru
Uday
U
Rouse
Barry T
BT
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D018259:Herpesvirus 1, Human / Q000276:immunology*; D016130:Immunophenotyping; D007165:Immunosuppression Therapy; D016849:Keratitis, Herpetic / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D008212:Lymphocyte Depletion; D008231:Lymphopenia / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D015375:Receptors, Interleukin-2 / Q000008:administration & dosage / Q000096:biosynthesis*; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000637:transplantation
D015375:Receptors, Interleukin-2