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IL-10 Regulates Movement of Intestinally Derived CD4⁺ T Cells to the Liver¹

Susan K. Bliss^2,*, Stuart P. Bliss, Daniel P. Beiting^*, Ana Alcaraz and Judith A. Appleton^*

^* James A. Baker Institute for Animal Health and Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853

Diseases that affect the intestine may have hepatic manifestations, but the mechanisms involved in establishing hepatic disease secondarily remain poorly understood. We previously reported that IL-10 knockout (KO) mice developed severe necrotizing hepatitis following oral infection with Trichinella spiralis. In this study, we used this model of intestinal inflammation to further examine the role of IL-10 in regulating hepatic injury. Hepatic damage was induced by migrating newborn larvae. By delivering the parasite directly into the portal vein, we demonstrated that an ongoing intestinal immune response was necessary for the development of hepatitis. Intestinally derived CD4⁺ cells increased in the livers of IL-10 KO mice, and Ab-mediated blockade of MAdCAM-1 inhibited the accumulation of CD4⁺₄₇⁺ cells in the liver. Moreover, adoptive transfer of intestinally primed CD4⁺ T cells from IL-10 KO mice caused hepatitis in infected immunodeficient animals. Conversely, transfer of wild-type donor cells reduced the severity of hepatic inflammation in IL-10 KO recipients, demonstrating regulatory activity. Our results revealed that IL-10 prevented migration of intestinal T cells to the liver and inhibited the development of hepatitis.

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 by National Institutes of Health Grants AI 14490 (to J.A.A.) and DK 67290 (to S.K.B.).

² Address correspondence and reprint requests to Dr. Susan K. Bliss, James A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853. E-mail address: spk2{at}cornell.edu

³ Abbreviations used in this paper: Tr1, type 1 regulatory T; ALT, alanine aminotransferase; ES, excretory-secretory; KO, knockout; L1, first-stage larvae; NBL, newborn larvae; WT, wild type.

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