title: Regulatory T cells participate in 4-1BB-mediated suppression of experimental allergic conjunctivitis.
abstract: BACKGROUND
  We showed previously that treatment with an agonistic anti-4-1BB Ab during the induction phase of murine experimental allergic conjunctivitis (EC) suppresses the development of this model disease. It was reported that 4-1BB promotes the expansion of regulatory T cells. Here we asked whether the suppression of EC by agonistic anti-4-1BB Ab treatment is mediated by regulatory T cells.
  
  
  METHODS
  Neonatal BALB/c mice were thymectomized and intraperitoneally injected with anti-CD25 Ab. At 6 weeks of age, these mice were immunized with ragweed (RW) in alum. As a control, immunocompetent BALB/c mice were immunized. Ten days later, the mice were challenged with RW in eye drops and 24 h later, the conjunctivas and spleens were harvested for histological and flow-cytometric analyses, respectively. The agonistic anti-4-1BB Ab or control normal rat IgG was injected intraperitoneally during the induction phase of EC.
  
  
  RESULTS
  With regard to immunocompetent mice, anti-4-1BB Ab treatment significantly suppressed the severity of EC as evaluated by conjunctival eosinophil numbers. In contrast, in thymectomized and anti-CD25 Ab-treated mice in which CD4+CD25+ regulatory T cells were efficiently depleted, anti-4-1BB Ab treatment did not affect the severity of EC.
  
  
  CONCLUSIONS
  These results indicate that CD4+CD25+ regulatory T cells play a critical role in the suppression of EC by anti-4-1BB Ab treatment.
authors.affiliation: Department of Ophthalmology, Kochi Medical School, Kohasu Oko-cho, Nankoku City, Japan.
authors.forename: Tamaki
authors.initials: T
authors.lastname: Sumi
authors.forename: Waka
authors.initials: W
authors.lastname: Ishida
authors.forename: Robert S
authors.initials: RS
authors.lastname: Mittler
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Osamu
authors.initials: O
authors.lastname: Taguchi
authors.forename: Atsuki
authors.initials: A
authors.lastname: Fukushima
mesh_terms: D031164:Ambrosia / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D003228:Conjunctiva / Q000166:cytology / Q000187:drug effects; D003233:Conjunctivitis, Allergic / Q000276:immunology* / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004804:Eosinophils / Q000166:cytology; D007114:Immunization; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011058:Pollen / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D013934:Thymectomy; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9