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PMID: 10562322 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Nonlymphocyte-derived tumor necrosis factor is required for induction of colitis in recombination activating gene (RAG)2(-/-) mice upon transfer of CD4(+)CD45RB(hi) T cells.

The Journal of experimental medicine ·Vol. 190 ·No. 10 ·1999-11-15 ·Pages 1479-92

Corazza N, Eichenberger S, Eugster HP, Mueller C

Abstract

In this study, we addressed the role of tumor necrosis factor (TNF)-alpha and lymphotoxin (LT)-alpha in the development of colitis and defined the cellular sources (T cells versus non-T cells) of TNF (TNF-alpha and LT-alpha) 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-gamma-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-alpha, as TNF-alpha(-/-)RAG2(-/-) recipients of TNF-alpha(-/-) 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-alpha in this mouse model of colitis.

MeSH Terms
Adoptive Transfer Animals CD4-Positive T-Lymphocytes/physiology DNA-Binding Proteins/genetics,physiology Inflammatory Bowel Diseases/etiology Interferon-gamma/physiology Leukocyte Common Antigens/physiology Mice Mice, Inbred C57BL Mice, Knockout RNA, Messenger/analysis Tumor Necrosis Factor-alpha/genetics,physiology
Chemicals
DNA-Binding Proteins RNA, Messenger Rag2 protein, mouse Tumor Necrosis Factor-alpha V(D)J recombination activating protein 2 Interferon-gamma Leukocyte Common Antigens
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Corazza N
Institute of Pathology, Division of Immunopathology, University of Bern, CH-3010 Bern, Switzerland.
Eichenberger S
Eugster H P
Mueller C
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.190.10.1479
Published
1999-11-15
Pages
1479-92
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2195702
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.190.10.1479 PMC Full Text View journal details
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