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

Iqbal N, Oliver JR, Wagner FH, Lazenby AS, Elson CO, Weaver CT - J. Exp. Med. (2002)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35233, USA.

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.

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Related in: MedlinePlus

Distribution of large intestinal disease mediated by Th1 and Th2 cells. The large intestines of pnir15.OVA-E. coli-colonized RAG-2−/− mice reconstituted with naive, Th1, or Th2 DO11.RAG-2−/− cells were subdivided into the indicated anatomical regions and evaluated histologically for disease involvement as in Table I.
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fig5: Distribution of large intestinal disease mediated by Th1 and Th2 cells. The large intestines of pnir15.OVA-E. coli-colonized RAG-2−/− mice reconstituted with naive, Th1, or Th2 DO11.RAG-2−/− cells were subdivided into the indicated anatomical regions and evaluated histologically for disease involvement as in Table I.

Mentions: At necropsy, macroscopic evaluation of animals from Th1 and Th2 groups colonized with pnir15.OVA-E. coli was remarkable for short, thickened large intestines. Focal superficial erythema and hemorrhages were present on cecal and colonic mucosal surfaces. The pnir15.TET-E. coli–colonized Th1 and Th2 groups were grossly normal, as were naive T cell recipients colonized with either pnir15.OVA-E. coli or pnir15.TET-E. coli. On microscopic evaluation, the large intestines from Th1 and Th2 groups colonized with pnir15.OVA-E. coli had moderate to severe disease characterized by extensive inflammatory cell infiltrates, marked epithelial cell hyperplasia and depletion of epithelial cell mucin (Fig. 4) . As shown in results from a representative experiment (Table I), the incidence and severity of disease was comparable in Th1 and Th2 groups. The distribution of involvement was also similar in Th1- and Th2-mediated disease (Fig. 5) , and was patchy along the length of the cecum and colon. Disease severity was modestly increased in colon compared with cecum; the rectum was spared. Although there was good population of the small intestinal LP with clonotypic T cells in all groups, no pathologic abnormalities were identified (data not shown). Similarly, there was no inflammation in other organs


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

Iqbal N, Oliver JR, Wagner FH, Lazenby AS, Elson CO, Weaver CT - J. Exp. Med. (2002)

Distribution of large intestinal disease mediated by Th1 and Th2 cells. The large intestines of pnir15.OVA-E. coli-colonized RAG-2−/− mice reconstituted with naive, Th1, or Th2 DO11.RAG-2−/− cells were subdivided into the indicated anatomical regions and evaluated histologically for disease involvement as in Table I.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196021&req=5

fig5: Distribution of large intestinal disease mediated by Th1 and Th2 cells. The large intestines of pnir15.OVA-E. coli-colonized RAG-2−/− mice reconstituted with naive, Th1, or Th2 DO11.RAG-2−/− cells were subdivided into the indicated anatomical regions and evaluated histologically for disease involvement as in Table I.
Mentions: At necropsy, macroscopic evaluation of animals from Th1 and Th2 groups colonized with pnir15.OVA-E. coli was remarkable for short, thickened large intestines. Focal superficial erythema and hemorrhages were present on cecal and colonic mucosal surfaces. The pnir15.TET-E. coli–colonized Th1 and Th2 groups were grossly normal, as were naive T cell recipients colonized with either pnir15.OVA-E. coli or pnir15.TET-E. coli. On microscopic evaluation, the large intestines from Th1 and Th2 groups colonized with pnir15.OVA-E. coli had moderate to severe disease characterized by extensive inflammatory cell infiltrates, marked epithelial cell hyperplasia and depletion of epithelial cell mucin (Fig. 4) . As shown in results from a representative experiment (Table I), the incidence and severity of disease was comparable in Th1 and Th2 groups. The distribution of involvement was also similar in Th1- and Th2-mediated disease (Fig. 5) , and was patchy along the length of the cecum and colon. Disease severity was modestly increased in colon compared with cecum; the rectum was spared. Although there was good population of the small intestinal LP with clonotypic T cells in all groups, no pathologic abnormalities were identified (data not shown). Similarly, there was no inflammation in other organs

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35233, USA.

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.

Show MeSH
Related in: MedlinePlus