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International Immunology Advance Access originally published online on February 28, 2008
International Immunology 2008 20(4):517-523; doi:10.1093/intimm/dxn017
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© The Japanese Society for Immunology. 2008. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Pervasive and stochastic changes in the TCR repertoire of regulatory T-cell-deficient mice

Lingjie Zheng1,*, Rahul Sharma2,*, John T. Kung3, Umesh S. Deshmukh2, Wael N. Jarjour4, Shu Man Fu1,2,4,{dagger} and Shyr-Te Ju1,2,{dagger}

1 Department of Microbiology and
2 Department of Medicine, Center for Immunity, Inflammation and Regenerative Medicine, University of Virginia, Charlottesville, VA 22908, USA
3 Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan, Republic of China
4 Department of Medicine, Division of Clinical Rheumatology, University of Virginia, Charlottesville, VA 22908, USA

Correspondence to: S.-T. Ju; E-mail: sj8r{at}virginia.edu

We hypothesize that regulatory T-cell (Treg)-deficient strains have an altered TCR repertoire in part due to the expansion of autoimmune repertoire by self-antigen. We compared the Vβ family expression profile between B6 and Treg-lacking B6.Cg-Foxp3sf/Y (B6.sf) mice using fluorescent anti-Vβ mAbs and observed no changes. However, while the spectratypes of 20 Vβ families among B6 mice were highly similar, the Vβ family spectratypes of B6.sf mice were remarkably different from B6 mice and from each other. Significant spectratype changes in many Vβ families were also observed in Treg-deficient IL-2 knockout (KO) and IL-2R{alpha} KO mice. Such changes were not observed with anti-CD3 mAb-treated B6 mice or B6 CD4+CD25– T cells. TCR transgenic (OT-II.sf) mice displayed dramatic reduction of clonotypic TCR with concomitant increase in T cells bearing non-transgenic Vβ and V{alpha} families, including T cells with dual receptors expressing reduced levels of transgenic V{alpha} and endogenous V{alpha}. Collectively, the data demonstrate that Treg deficiency allows polyclonal expansion of T cells in a stochastic manner, resulting in widespread changes in the TCR repertoire.

Keywords: autoimmunity, dual-TCR, repertoire, scurfy, T cells

* These authors contributed equally to this study.

{dagger} Senior authors contributed equally to this study.

Transmitting editor: R. Geha

Received 12 September 2007, accepted 22 January 2008.


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