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The Journal of Immunology, 2007, 178: 1039-1047.
Copyright © 2007 by The American Association of Immunologists, Inc.

Coordinated Control of Immunity to Muscle Stage Trichinella spiralis by IL-10, Regulatory T Cells, and TGF-beta1

Daniel P. Beiting*, Lucille F. Gagliardo*, Matthias Hesse{dagger}, Susan K. Bliss*, Diana Meskill* and Judith A. Appleton2,{dagger}

* James A. Baker Institute for Animal Health and {dagger} Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853

We previously demonstrated that IL-10 is critical in the control of acute inflammation during development of Trichinella spiralis in the muscle. In this study, we use gene-targeted knockout mice, adoptive transfer of specific T cell populations, and in vivo Ab treatments to determine the mechanisms by which inflammation is controlled and effector T cell responses are moderated during muscle infection. We report that CD4+CD25 effector T cells, rather than CD4+CD25+ regulatory T cells, suppress inflammation by an IL-10-dependent mechanism that limits IFN-{gamma} production and local inducible NO synthase induction. Conversely, we show that depletion of regulatory T cells during infection results in exaggerated Th2 responses. Finally, we provide evidence that, in the absence of IL-10, TGF-beta participates in control of local inflammation in infected muscle and promotes parasite survival.

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 This research was supported by a grant to J.A.A. from the National Institutes of Health (A114490). D.P.B. was supported by Training Grant T32-AI07643.

2 Address correspondence and reprint requests to Dr. Judith A. Appleton, James A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853. E-mail address: jaa2{at}cornell.edu

3 Abbreviations used in this paper: NBL, newborn larvae; Treg, regulatory T cell; Foxp3, forkhead box P3; Teff, effector T cell; KO, knockout; CLN, cervical lymph node; dpi, days postinjection; WT, wild type; iNOS, inducible NO synthase; 1°/2°, primary/secondary.




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