Journal article

Defects in the Bcl-2-Regulated Apoptotic Pathway Lead to Preferential Increase of CD25(low)Foxp3( ) Anergic CD4( ) T Cells

Yifan Zhan, Yuxia Zhang, Daniel Gray, Emma M Carrington, Philippe Bouillet, Hyun-Ja Ko, Lorraine O'Reilly, Ian P Wicks, Andreas Strasser, Andrew M Lew

JOURNAL OF IMMUNOLOGY | AMER ASSOC IMMUNOLOGISTS | Published : 2011

Abstract

Defects in the Bcl-2-regulated apoptotic pathway inhibit the deletion of self-reactive T cells. What is unresolved, however, is the nature and fate of such self-reactive T cells escaping deletion. In this study, we report that mice with such defects contained increased numbers of CD25(low)Foxp3(+) cells in the thymus and peripheral lymph tissues. The increased CD25(low)Foxp3(+) population contained a large fraction of cells bearing self-reactive TCRs, evident from a prominent increase in self-superantigen-specific Foxp3(+)Vβ5(+)CD4(+) T cells in BALB/c Bim(-/-) mice compared with control animals. The survival rate of the expanded CD25(low)Foxp3(+) cells was similar to that of CD25(high)Foxp3..

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Grants

Awarded by National Health and Medical Research Council of Australia


Awarded by National Health and Medical Research Council


Awarded by National Institutes of Health


Awarded by Leukemia and Lymphoma Society (LLS)


Awarded by Juvenile Diabetes Research Foundation


Awarded by NATIONAL CANCER INSTITUTE


Funding Acknowledgements

This work was supported by National Health and Medical Research Council of Australia Program Grants 516700 and 461221, Project Grants 575543 and 637324, National Health and Medical Research Council Australia Fellowship 461299, National Health and Medical Research Council Career Development Awards 516754 and 637353, National Health and Medical Research Council Independent Research Institutes Infrastructure Support Scheme Grant 361646, the National Institutes of Health (CA 043540), the Leukemia and Lymphoma Society (LLS SCOR 7413), Juvenile Diabetes Research Foundation Grant 466658, and a Victorian State Government Operational Infrastructure Support grant.