Granzyme B regulates antiviral CD8+ T cell responses. J Immunol 2011 Dec 15;187(12):6301-9
Date
11/16/2011Pubmed ID
22084442Pubmed Central ID
PMC3237805DOI
10.4049/jimmunol.1100891Scopus ID
2-s2.0-83755178618 (requires institutional sign-in at Scopus site) 60 CitationsAbstract
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.
Author List
Salti SM, Hammelev EM, Grewal JL, Reddy ST, Zemple SJ, Grossman WJ, Grayson MH, Verbsky JWAuthor
James Verbsky MD, PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCD8-Positive T-Lymphocytes
Epitopes, T-Lymphocyte
Granzymes
Lung
Lymph Nodes
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Perforin
Respirovirus Infections
Sendai virus
T-Lymphocytes, Regulatory
Viral Load
Weight Loss
