Journal article

Granzyme B Is Dispensable in the Development of Diabetes in Non-Obese Diabetic Mice

Zia U Mollah, Kate L Graham, Balasubramanian Krishnamurthy, Prerak Trivedi, Thomas C Brodnicki, Joseph A Trapani, Thomas W Kay, Helen E Thomas

PLOS ONE | PUBLIC LIBRARY SCIENCE | Published : 2012

Abstract

Pancreatic beta cell destruction in type 1 diabetes is mediated by cytotoxic CD8(+) T lymphoctyes (CTL). Granzyme B is an effector molecule used by CTL to kill target cells. We previously showed that granzyme B-deficient allogeneic CTL inefficiently killed pancreatic islets in vitro. We generated granzyme B-deficient non-obese diabetic (NOD) mice to test whether granzyme B is an important effector molecule in spontaneous type 1 diabetes. Granzyme B-deficient islet antigen-specific CD8(+) T cells had impaired homing into islets of young mice. Insulitis was reduced in granzyme B-deficient mice at 70 days of age (insulitis score 0.043±0.019 in granzyme B-deficient versus 0.139±0.034 in wild-typ..

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Grants

Awarded by National Health and Medical Research Council of Australia (NHMRC): NHMRC/JDRF special program grant in type 1 diabetes


Awarded by NHMRC Career Development Fellowship


Awarded by NHMRC


Awarded by Juvenile Diabetes Research Foundation (JDRF): JDRF Postdoctoral Fellowship


Awarded by JDRF Postdoctoral Fellowship


Funding Acknowledgements

This work was funded by National Health and Medical Research Council of Australia (NHMRC) (http://www.nhmrc.gov.au/): NHMRC/JDRF special program grant in type 1 diabetes APP466658; NHMRC project grant APP502605; NHMRC Career Development Fellowship (HT) APP620232; Juvenile Diabetes Research Foundation (JDRF) http://www.jdrf.org/): JDRF Postdoctoral Fellowship (ZM) 4-2006-1025; JDRF Postdoctoral Fellowship (KG) 4-2006-1025; JDRF Career Development Award (BK); The Victorian Government's Operational Infrastructure Support Program (http://www.business.vic.gov.au/BUSVIC/STANDARD/PC_60698.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.