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Th1, Th2, and Th17 Effector T Cell-Induced Autoimmune Gastritis Differs in Pathological Pattern and in Susceptibility to Suppression by Regulatory T Cells¹

Georg H. Stummvoll^*, Richard J. DiPaolo^*, Eva N. Huter^*, Todd S. Davidson^*, Deborah Glass^*, Jerrold M. Ward and Ethan M. Shevach^2,*

^* Laboratory of Immunology, Cellular Immunology Section and Comparative Medicine Branch, Infectious Disease Pathogenesis Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892

Th cells can be subdivided into IFN--secreting Th1, IL-4/IL-5-secreting Th2, and IL-17-secreting Th17 cells. We have evaluated the capacity of fully differentiated Th1, Th2, and Th17 cells derived from a mouse bearing a transgenic TCR specific for the gastric parietal cell antigen, H⁺K⁺-ATPase, to induce autoimmune gastritis after transfer to immunodeficient recipients. We have also determined the susceptibility of the disease induced by each of the effector T cell types to suppression by polyclonal regulatory T cells (Treg) in vivo. Each type of effector cell induced autoimmune gastritis with distinct histological patterns. Th17 cells induced the most destructive disease with cellular infiltrates composed primarily of eosinophils accompanied by high levels of serum IgE. Polyclonal Treg could suppress the capacity of Th1 cells, could moderately suppress Th2 cells, but could suppress Th17-induced disease only at early time points. The major effect of the Treg was to inhibit the expansion of the effector T cells. However, effector cells isolated from protected animals were not anergic and were fully competent to proliferate and produce effector cytokines ex vivo. The strong inhibitory effect of polyclonal Treg on the capacity of some types of differentiated effector cells to induce disease provides an experimental basis for the clinical use of polyclonal Treg in the treatment of autoimmune disease in humans.

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 work was supported funds from the intramural program of the National Institute of Allergy and Infectious Diseases and by a Max Kade Foundation Postdoctoral Research Exchange Grant (to G.H.S.).

² Address correspondence and reprint requests to Dr. Ethan M. Shevach, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10 Room 11N315, Bethesda, MD 20892. E-mail address: eshevach{at}niaid.nih.gov

³ Abbreviations used in this paper: AIG, autoimmune gastritis; Tg, transgenic; Treg, regulatory T cell; gLN, gastric lymph node; CD62L, L-selectin.

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The JI 2008 181: 1593-1594. [Full Text]