title: The effect of CTLA-4Ig, a CD28/B7 antagonist, on the lung inflammation and T cell subset profile during murine hypersensitivity pneumonitis.
abstract: Hypersensitivity pneumonitis (HP) is an inflammatory lung disease characterized by an influx of activated T cells to the lung, in which the CD28/B7 costimulatory signals are essential for the T cell activation and the outcome of the inflammatory response. In this study, we investigated the effect of the CD28/B7 antagonist, CTLA-4Ig, on the lung inflammation and the T cell subset profile in experimental Saccharopolyspora recivirgula (SR)-induced HP. C57BL/6 mice were treated with SR or saline during two and three weeks and in addition of CTLA-4Ig was administrated after either the second or third week and mice were sacrificed seven days later. The extent of the lung inflammation was quantified by histopathology and the lung T cell subsets (Treg, Th17, γδT and NKT) were analyzed by flow cytometry. Mice treated with CTLA-4Ig showed a significant decrease in the extent of lung damage (p<0.05), and exhibited a decreased number of inflammatory cells in the bronchoalveolar lavage (BAL) with diminished CD4/CD8 T cell ratio. Also, a significant increase in the percentage of lung γδT (p<0.01) and NKT (p<0.05) cells was observed in two weeks SR-treated mice with the administration of CTLA-4Ig/SR. At 3 weeks, SR-treated mice showed an increased percentage of regulatory T cells but no significantly differences were found in the percentage of Th17 cells when compared with CTLA-4Ig/SR-treated mice. Our findings suggest that the treatment with CTLA-4Ig affects the HP progression and the lung T cell subset kinetics in mice.
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.
authors.forename: Luis
authors.initials: L
authors.lastname: Jiménez-Alvarez
authors.forename: José Luis
authors.initials: JL
authors.lastname: Arreola
authors.forename: Gustavo
authors.initials: G
authors.lastname: Ramírez-Martínez
authors.forename: Blanca
authors.initials: B
authors.lastname: Ortiz-Quintero
authors.forename: Miguel
authors.initials: M
authors.lastname: Gaxiola
authors.forename: Rafael
authors.initials: R
authors.lastname: Reynoso-Robles
authors.forename: Federico
authors.initials: F
authors.lastname: Avila-Moreno
authors.forename: Francisco
authors.initials: F
authors.lastname: Urrea
authors.forename: Annie
authors.initials: A
authors.lastname: Pardo
authors.forename: Moisés
authors.initials: M
authors.lastname: Selman
authors.forename: Joaquín
authors.initials: J
authors.lastname: Zuñiga
mesh_terms: D000069594:Abatacept; D000542:Alveolitis, Extrinsic Allergic / Q000188:drug therapy / Q000276:immunology; D000818:Animals; D060887:B7 Antigens / Q000037:antagonists & inhibitors* / Q000276:immunology; D018106:CD28 Antigens / Q000037:antagonists & inhibitors* / Q000276:immunology; D018450:Disease Progression; D005260:Female; D018796:Immunoconjugates / Q000494:pharmacology*; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology
chemical_list: D060887:B7 Antigens; D018106:CD28 Antigens; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D000069594:Abatacept