title: Fas/FasL and perforin-granzyme pathways mediated T cell cytotoxic responses in infectious bursal disease virus infected chickens.
abstract: Infectious bursal disease (IBD) is a highly contagious disease of chickens which leads to immunosuppression. In our previous study it was demonstrated that, possibly, CD4(+) and CD8(+) T cells may employ perforin and granzyme-A pathway for the clearance of IBDV-infected bursal cells. In this study, we evaluated the cytotoxic T cell responses involving two independently functioning but complementary mechanisms: Fas-Fas ligand and perforin-granzyme pathways in IBDV-infected chickens. As demonstrated previously, infection of chickens with IBDV was accompanied by influx of CD8(+) T cells in the bursa and spleen. There was an upregulation in the gene expression of cytolytic molecules: Fas and Fas ligand (FasL), perforin (PFN) and granzyme-A (Gzm-A) in bursal and in the splenic tissues of IBDV inoculated chickens. Additionally, for the first time, we detected Fas, Fas ligand, Caspase-3 and PFN producing CD8(+) T cells in the bursa and spleen of IBDV-infected chickens. The infiltration and activation of CD8(+) T cells was substantiated by the detection of Th1 cytokine, IFN-γ. These data suggest that T cells may be involved in the clearance of virus from the target organ bursa and peripheral tissues such as spleen. The findings of these studies provide new insights into the pathogenesis of IBD and provide mechanistic evidence that the cytotoxic T cells may act through both Fas-FasL and perforin-granzyme pathways in mediating the clearance of virus-infected cells.
authors.affiliation: Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, 1680 Madison Avenue, Wooster, OH 44691, United States.
authors.forename: Abdul
authors.initials: A
authors.lastname: Rauf
authors.affiliation: Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, 1680 Madison Avenue, Wooster, OH 44691, United States.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Khatri
authors.affiliation: Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, 1680 Madison Avenue, Wooster, OH 44691, United States ; Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Maria V
authors.initials: MV
authors.lastname: Murgia
authors.affiliation: Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, 1680 Madison Avenue, Wooster, OH 44691, United States ; Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Yehia M
authors.initials: YM
authors.lastname: Saif
keywords: Bursa of Fabricius, BF; Classical Infectious Bursal Disease Virus, cIBDV; Cytotoxic T Lymphocytes, CTLs; Cytotoxic T cells; Fas Ligand, FasL; Fas–FasL; Gamma Interferon, IFN-γ; Granzyme; Granzyme, Gzm; IBDV; Perforin; Perforin, PFN; Post Inoculation Days, PIDs; Quantitative RT-PCR, qRT-PCR; Tumor Necrosis Factor, TNF; Virus clearance