Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 203, Issue 13, Pages 2785-2791Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20061341
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Funding
- NIAID NIH HHS [P01 AI035297, R01 AI064677, P01 AI35297, R01 AI64677] Funding Source: Medline
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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.
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