The Journal of Experimental Medicine
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Published online November 27, 2006
doi:10.1084/jem.20061341
The Journal of Experimental Medicine, Vol. 203, No. 13, 2785-2791
The Rockefeller University Press, 0022-1007 $30.00
© 2006 Lohr et al.
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BRIEF DEFINITIVE REPORT

 Role of IL-17 and regulatory T lymphocytes in a systemic autoimmune disease

Jens Lohr1,2, Birgit Knoechel1,3, Jing Jing Wang1, Alejandro V. Villarino1, and Abul K. Abbas1

1 Department of Pathology, 2 Department of Medicine, 3 Department of Pediatrics, University of California, San Francisco School of Medicine, San Francisco, CA 94143

CORRESPONDENCE Abul K. Abbas: abul.abbas{at}ucsf.edu

To explore the interactions between regulatory T cells and pathogenic effector cytokines, we have developed a model of a T cell–mediated systemic autoimmune disorder resembling graft-versus-host disease. The cytokine responsible for tissue inflammation in this disorder is interleukin (IL)-17, whereas interferon (IFN)-{gamma} produced by Th1 cells has a protective effect in this setting. Because of the interest in potential therapeutic approaches utilizing transfer of regulatory T cells and inhibition of the IL-2 pathway, we have explored the roles of these in the systemic disease. We demonstrate that the production of IL-17 and tissue infiltration by IL-17–producing cells occur and are even enhanced in the absence of IL-2. Regulatory T cells favor IL-17 production but prevent the disease when administered early in the course by suppressing expansion of T cells. Thus, the pathogenic or protective effects of cytokines and the therapeutic capacity of regulatory T cells are crucially dependent on the timing and the nature of the disease.

J. Lohr and B. Knoechel contributed equally to this work.


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