The Journal of Experimental Medicine
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Published online 30 January 2006 doi:10.1084/jem.20051438
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 2, 349-358
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ARTICLE

 B cell–deficient NOD.H-2h4 mice have CD4+CD25+ T regulatory cells that inhibit the development of spontaneous autoimmune thyroiditis

Shiguang Yu1, Prasanta K. Maiti1, Melissa Dyson3, Renu Jain2, and Helen Braley-Mullen1,2,4

1 Department of Medicine, 2 Department of Molecular Microbiology and Immunology, 3 Department of Veterinary Pathobiology, and 4 VA Research Service, University of Missouri, Columbia, MO 65212

CORRESPONDENCE Helen Braley-Mullen: mullenh{at}health.missouri.edu

Wild-type (WT) NOD.H-2h4 mice develop spontaneous autoimmune thyroiditis (SAT) when given 0.05% NaI in their drinking water, whereas B cell–deficient NOD.H-2h4 mice are SAT resistant. To test the hypothesis that resistance of B cell–deficient mice to SAT was due to the activity of regulatory CD4+CD25+ T (T reg) cells activated if autoantigen was initially presented on non–B cells, CD25+ T reg cells were transiently depleted in vivo using anti-CD25. B cell–deficient NOD.H-2h4 mice given three weekly injections of anti-CD25 developed SAT 8 wk after NaI water. Thyroid lesions were similar to those in WT mice except there were no B cells in thyroid infiltrates. WT and B cell–deficient mice had similar numbers of CD4+CD25+Foxp3+ cells. Mice with transgenic nitrophenyl-specific B cells unable to secrete immunoglobulin were also resistant to SAT, and transient depletion of T reg cells resulted in severe SAT with both T and B cells in thyroid infiltrates. T reg cells that inhibit SAT were eliminated by day 3 thymectomy, indicating they belong to the subset of naturally occurring T reg cells. However, T reg cell depletion did not increase SAT severity in WT mice, suggesting that T reg cells may be nonfunctional when effector T cells are activated; i.e., by autoantigen-presenting B cells.

Abbreviations used: MTg, mouse thyroglobulin; NOD, nonobese diabetic; NP, nitrophenyl; SAT, spontaneous autoimmune thyroiditis; Tg, transgenic; T reg, regulatory T; Tx, thymectomy.


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