Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 600K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Corazza, N. Articles by Mueller, C. Search for Related Content PubMed PubMed Citation Articles by Corazza, N. Articles by Mueller, C. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Social Bookmarking                            What's this?

Original Article

^a Institute of Pathology, Division of Immunopathology, University of Bern, CH-3010 Bern, Switzerland
^b Department of Internal Medicine, University Hospital Zurich, CH-8057 Zurich, Switzerland
Institute of Pathology, Div. of Immunopathology, Murtenstrasse 31, CH-3010 Bern, Switzerland.41-31-381-87-6441-31-632-89-04

christoph.mueller{at}pathology.unibe.ch

In this study, we addressed the role of tumor necrosis factor (TNF)- and lymphotoxin (LT)- in the development of colitis and defined the cellular sources (T cells versus non-T cells) of TNF (TNF- and LT-) relevant to disease development. After adoptive transfer of TNF^+/+ CD4⁺CD45RB^hi splenocytes into TNF^+/+ recombination activating gene (RAG)2^–/– mice, the recipients develop massive inflammation of the large intestinal mucosa concurrent with massive weight loss. In contrast, clinical signs of disease are completely absent in TNF^–/–RAG2^–/– recipients of TNF^–/– CD4⁺CD45RB^hi T cells, although elevated numbers of interferon-–producing cells are present in the colonic mucosa. Surprisingly, upon transfer of TNF^–/–CD4⁺CD45RB^hi T cells into TNF^+/+RAG2^–/– recipients, colitis develops with kinetics similar to those upon transfer of TNF^+/+CD4⁺CD45RB^hi donor cells. In contrast, no clinical signs of colitis are observed in TNF^–/–RAG2^–/– recipients of TNF^+/+CD4⁺CD45RB^hi T cells. This protection from colitis is not a consequence of the absence of LT-, as TNF-^–/–RAG2^–/– recipients of TNF-^–/– CD4⁺CD45RB^hi T cells are also protected from colitis induction. These results demonstrate the importance of TNF production by non-T cells of the colonic mucosa in the pathogenesis of colitis and provide direct evidence for a nonredundant role of TNF- in this mouse model of colitis.

Key Words: inflammatory bowel disease • mucosal immunity • intestinal inflammation • proinflammatory cytokines

© 1999 The Rockefeller University Press

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS