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Cutting Edge: Autoimmune Disease in Day 3 Thymectomized Mice Is Actively Controlled by Endogenous Disease-Specific Regulatory T Cells¹

Eileen T. Samy^2,3,*, Karen M. Wheeler^2,*, Randall J. Roper, Cory Teuscher and Kenneth S. K. Tung^4,*

^* Department of Pathology, University of Virginia, Charlottesville, VA 22908; Department of Biology, Indiana University-Purdue University, Indianapolis, Indianapolis, IN 46202; and Department of Medicine and Pathology, University of Vermont, Burlington, VT 05405

Female B6AF1 mice thymectomized on day 3 (d3tx) develop autoimmune ovarian disease (AOD) and dacryoadenitis. It has been hypothesized that d3tx breaks tolerance by depleting late ontogeny regulatory T cells (Treg). We now report that Treg greatly expand over effector T cells in d3tx mice and adoptively suppress autoimmune disease in d3tx recipients. In the d3tx donors, Treg from ovarian lymph nodes (LN) preferentially suppress AOD and Treg from lacrimal gland LN preferentially suppress dacryoadenitis, suggesting they are strategically positioned for disease control. Indeed, the autologous disease in d3tx mice is dramatically enhanced by in vivo depletion of endogenous Treg. Moreover, normal 3-day-old mice possess Treg that suppress AOD and autoimmune gastritis as efficiently as adult cells. Thus, d3tx mice possess disease-relevant Treg of presumed neonatal origin. They accumulate in the regional LN and actively inhibit concurrent autoimmune disease; however, they cannot fully prevent autoimmune disease development.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ The study was supported by National Institutes of Health Grants AI 41236, AI 51420, and AI 4174.

² E.T.S. and K.M.W. contributed equally to this study.

³ Current address: Inflammation Discovery, Roche Palo Alto LLC, Palo Alto, CA 94304.

⁴ Address correspondence and reprint requests to Dr. Kenneth S. K. Tung, University of Virginia Health System, Box 800168, Charlottesville, VA 22908. E-mail address: kst7k{at}virginia.edu

⁵ Abbreviations used in this paper: Treg, regulatory T cell; AOD, autoimmune ovarian disease; AIG, autoimmune gastritis, DA, dacryoadenitis; d3tx, day 3 thymectomy; Foxp3, Forkhead box p3; LN, lymph node.