title: On the role of regulatory T cells during viral-induced inflammatory lesions.
abstract: Ocular HSV-1 infection can result in stromal keratitis, a blinding immunoinflammatory lesion that represents an immunopathological response to the infection. CD4(+) T cells are the main orchestrators, and lesions are more severe if the regulatory T cell (Treg) response is compromised from the onset of infection. Little is known about the role of Foxp3(+)CD4(+) Tregs during ongoing inflammatory reactions, which is the topic of this article. We used DEREG mice and depleted Tregs at different times postinfection. We show that lesions became more severe even when depletion was begun in the clinical phase of the disease. This outcome was explained both by Tregs' influence on the activity of inflammatory effector T cells at the lesion site and by an effect in lymphoid tissues that led to reduced numbers of effectors and less trafficking of T cells and neutrophils to the eye. Our results demonstrate that Tregs can beneficially influence the impact of ongoing tissue-damaging responses to a viral infection and imply that therapies boosting Treg function in the clinical phase hold promise for controlling a lesion that is an important cause of human blindness.
authors.affiliation: Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.
authors.forename: Tamara
authors.initials: T
authors.lastname: Veiga-Parga
authors.forename: Amol
authors.initials: A
authors.lastname: Suryawanshi
authors.forename: Sachin
authors.initials: S
authors.lastname: Mulik
authors.forename: Fernanda
authors.initials: F
authors.lastname: Giménez
authors.forename: Shalini
authors.initials: S
authors.lastname: Sharma
authors.forename: Tim
authors.initials: T
authors.lastname: Sparwasser
authors.forename: Barry T
authors.initials: BT
authors.lastname: Rouse
mesh_terms: D000818:Animals; D051858:Forkhead Transcription Factors / Q000235:genetics; D017930:Genes, Reporter / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000276:immunology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000821:virology; D016849:Keratitis, Herpetic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008198:Lymph Nodes; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology / Q000821:virology
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse