T helper 1 and T helper 2 cells are pathogenic in an antigen-specific model of colitis

Nuzhat Iqbal, James R. Oliver, Frederic H. Wagner, Audrey S. Lazenby, Charles O. Elson, Casey T. Weaver

Research output: Contribution to journalArticle

119 Scopus citations

Abstract

Dysregulated T cell responses to enteric bacteria have been implicated as a common mechanism underlying pathogenesis in rodent models of colitis. However, the bacterial species and T cell specificities that induce disease have been poorly defined. We have developed a model system in which target antigen, bacterial host, and corresponding T cell specificity are defined. OVA-specific T cells from DO11.RAG-2-/- TCR transgenic mice were transferred into RAG-2-/- recipients whose intestinal tracts were colonized with OVA-expressing or control Escherichia coli. Transfer of antigen-naive DO11.RAG-2-/- T cells into recipients colonized with OVA-E. coli resulted in enhanced intestinal recruitment and cell cycling of OVA-specific T cells; however, there was no development of disease. In contrast, transfer of polarized T helper (Th) 1 and Th2 populations resulted in severe wasting and colitis in recipients colonized with OVA-expressing but not control E. coli. The histopathologic features of disease induced by Th1 and Th2 transfers were distinct, but disease severity was comparable. Induction of disease by both Th1 and Th2 transfers was dependent on bacterially associated OVA. These results establish that a single bacterially associated antigen can drive the progression of colitis mediated by both Th1 and Th2 cells and provide a new model for understanding the immunoregulatory interactions between T cells responsive to gut floral antigens.

Original languageEnglish (US)
Pages (from-to)71-84
Number of pages14
JournalJournal of Experimental Medicine
Volume195
Issue number1
DOIs
StatePublished - Jan 7 2002

Keywords

  • CD4
  • Cytokines
  • E. coli
  • Inflammatory bowel disease
  • TCR transgenic

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'T helper 1 and T helper 2 cells are pathogenic in an antigen-specific model of colitis'. Together they form a unique fingerprint.

  • Cite this