Epitopes described in "Granzyme B regulates antiviral CD8+ T cell responses."

Article Authors:Suzan M Salti; Erin M Hammelev; Jenny L Grewal; Sreelatha T Reddy; Sarah J Zemple; William J Grossman; Mitchell H Grayson; James W Verbsky
Article Title:Granzyme B regulates antiviral CD8+ T cell responses.
Reference Detail
Reference ID:1022815
Abstract:CTLs and NK cells use the perforin/granzyme cytotoxic pathway to kill virally infected cells and tumors. Human regulatory T cells also express functional granzymes and perforin and can induce autologous target cell death in vitro. Perforin-deficient mice die of excessive immune responses after viral challenges, implicating a potential role for this pathway in immune regulation. To further investigate the role of granzyme B in immune regulation in response to viral infections, we characterized the immune response in wild-type, granzyme B-deficient, and perforin-deficient mice infected with Sendai virus. Interestingly, granzyme B-deficient mice, and to a lesser extent perforin-deficient mice, exhibited a significant increase in the number of Ag-specific CD8(+) T cells in the lungs and draining lymph nodes of virally infected animals. This increase was not the result of failure in viral clearance because viral titers in granzyme B-deficient mice were similar to wild-type mice and significantly less than perforin-deficient mice. Regulatory T cells from WT mice expressed high levels of granzyme B in response to infection, and depletion of regulatory T cells from these mice resulted in an increase in the number of Ag-specific CD8(+) T cells, similar to that observed in granzyme B-deficient mice. Furthermore, granzyme B-deficient regulatory T cells displayed defective suppression of CD8(+) T cell proliferation in vitro. Taken together, these results suggest a role for granzyme B in the regulatory T cell compartment in immune regulation to viral infections.
Affiliations:Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Reference Type:Literature
PubMed ID:22084442
Journal:J Immunol
Journal Volume:187
Article Pages:6301-9
Journal ISSN:0022-1767
Article Chemical List:Epitopes, T-Lymphocyte;Perforin;Granzymes;Gzmb protein, mouse
Article MeSH List:Animals; CD8-Positive T-Lymphocytes(immunology; pathology; virology); Epitopes, T-Lymphocyte(genetics; immunology); Granzymes(deficiency; genetics; physiology); Lung(immunology; pathology; virology); Lymph Nodes(immunology; pathology; virology); Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Perforin(deficiency; genetics); Respirovirus Infections(immunology; pathology; virology); Sendai virus(immunology); T-Lymphocytes, Regulatory(enzymology; immunology; virology); Viral Load(genetics; immunology); Weight Loss(genetics; immunology)
Curation Last Updated:2015-07-30 20:44:55