title: IL-2/anti-IL-2 antibody complex treatment inhibits the development but not the progression of herpetic stromal keratitis.
abstract: The IL-2/anti-IL-2 Ab immunocomplex has recently been shown to expand the naturally occurring pool of CD4(+)Foxp3(+) regulatory T cells (Tregs). In this study, we show that administration of the IL-2/anti-IL-2 Ab immunocomplex to C57BL/6 mice, prior to corneal HSV-1 infection, significantly increased the pool of Foxp3(+) Tregs when measured at early time points postinfection. Increased numbers of Foxp3(+) Tregs on days 2 and 4 postinfection resulted in a marked reduction in the development of severe herpetic stromal keratitis (HSK). When compared with corneas from the control group, corneas from the immunocomplex-treated group showed a significant reduction in the amount of infectious virus on day 2 but not on day 4 postinfection. Reduced viral load was associated with a 2-fold increase in NK cell numbers in corneas from the immunocomplex-treated group of mice. Moreover, a dramatic reduction in the influx of CD4 T cells in inflamed corneas was determined on days 7 and 16 postinfection in the immunocomplex-treated group of infected mice. Immunocomplex treatment given on days 5, 6, and 7 postinfection significantly increased Foxp3(+) Tregs in draining lymph nodes and in the spleen but failed to reduce the severity of HSK. In terms of the influx of CD4 T cells and granulocytes into inflamed corneas, no significant differences were noted between both groups of mice on day 16 postinfection. Our findings demonstrate that increasing Foxp3(+) Tregs early but not late postinfection in secondary lymphoid tissues is more efficacious in controlling the severity of HSK.
authors.affiliation: Department of Biological Sciences, Oakland University, Rochester, MI 48309; Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI 48201; Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201; and.
authors.forename: Subhash
authors.initials: S
authors.lastname: Gaddipati
authors.affiliation: Department of Biological Sciences, Oakland University, Rochester, MI 48309; Michigan State University College of Human Medicine, East Lansing, MI 48824.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Estrada
authors.affiliation: Department of Biological Sciences, Oakland University, Rochester, MI 48309; Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI 48201; Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201; and.
authors.forename: Pushpa
authors.initials: P
authors.lastname: Rao
authors.affiliation: Department of Biological Sciences, Oakland University, Rochester, MI 48309; Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI 48201; Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201; and.
authors.forename: Andrew David
authors.initials: AD
authors.lastname: Jerome
authors.affiliation: Department of Biological Sciences, Oakland University, Rochester, MI 48309; Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI 48201; Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201; and ssuvas@med.wayne.edu.
authors.forename: Susmit
authors.initials: S
authors.lastname: Suvas
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D002465:Cell Movement / Q000276:immunology; D003315:Cornea / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018450:Disease Progression; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D006098:Granulocytes / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000276:immunology*; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000627:therapeutic use*; D016849:Keratitis, Herpetic / Q000473:pathology / Q000628:therapy*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D019562:Viral Load / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2; D007371:Interferon-gamma