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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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Histological analyses of colonic tissues from mice with Th1- or Th2-mediated colitis. Paraffin-embedded sections of colon from the indicated experimental groups were processed and stained as described in Materials and Methods. (A) Th1- and Th2-reconstituted/pnir15.OVA-E. coli-colonized, serial sections of proximal colon stained with anti-CD3 to identify T cells (left, top, and bottom) or Leder stain to identify neutrophils and eosinophils (right, top, and bottom). Arrows identify intraepithelial Th1 cells in diseased proximal colon. (B) Proximal colon from naive-reconstituted RAG-2−/− mice colonized with pnir15.TET-E. coli (top) or pnir15.OVA-E. coli mice (bottom) stained with anti-CD3. (C) Low and high power images of Th1-reconstituted/pnir15.OVA-E. coli–colonized middle colon double-labeled with anti-CD3 (brown) and anti-BrdU (red). Arrowheads identify CD3+ DO11.RAG-2−/− T cells that have incorporated BrdU after 9 d in vivo administration. Note also the incorporation of BrdU by colonic crypt epithelial cells.
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fig6: Histological analyses of colonic tissues from mice with Th1- or Th2-mediated colitis. Paraffin-embedded sections of colon from the indicated experimental groups were processed and stained as described in Materials and Methods. (A) Th1- and Th2-reconstituted/pnir15.OVA-E. coli-colonized, serial sections of proximal colon stained with anti-CD3 to identify T cells (left, top, and bottom) or Leder stain to identify neutrophils and eosinophils (right, top, and bottom). Arrows identify intraepithelial Th1 cells in diseased proximal colon. (B) Proximal colon from naive-reconstituted RAG-2−/− mice colonized with pnir15.TET-E. coli (top) or pnir15.OVA-E. coli mice (bottom) stained with anti-CD3. (C) Low and high power images of Th1-reconstituted/pnir15.OVA-E. coli–colonized middle colon double-labeled with anti-CD3 (brown) and anti-BrdU (red). Arrowheads identify CD3+ DO11.RAG-2−/− T cells that have incorporated BrdU after 9 d in vivo administration. Note also the incorporation of BrdU by colonic crypt epithelial cells.

Mentions: The histologic features of disease in Th1 and Th2 recipient mice colonized with pnir15.OVA-E. coli were distinct. The lesions in mice that received Th1 cells were characterized by predominantly mononuclear cell infiltrates composed of lymphocytes and monocytes/macrophages that expanded the LP and distorted the crypt architecture (Fig. 6 and Table II). Focally, there was extension of the inflammation into the underlying muscularis and serosa. Scattered, small granulomas were evident, but were not a dominant feature. Frequent crypt abscesses were evident, and T cells invaded the epithelium. Neutrophils were present in the areas of most severe epithelial injury, particularly bordering and infiltrating damaged crypts. Eosinophils were rarely seen.


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)

Histological analyses of colonic tissues from mice with Th1- or Th2-mediated colitis. Paraffin-embedded sections of colon from the indicated experimental groups were processed and stained as described in Materials and Methods. (A) Th1- and Th2-reconstituted/pnir15.OVA-E. coli-colonized, serial sections of proximal colon stained with anti-CD3 to identify T cells (left, top, and bottom) or Leder stain to identify neutrophils and eosinophils (right, top, and bottom). Arrows identify intraepithelial Th1 cells in diseased proximal colon. (B) Proximal colon from naive-reconstituted RAG-2−/− mice colonized with pnir15.TET-E. coli (top) or pnir15.OVA-E. coli mice (bottom) stained with anti-CD3. (C) Low and high power images of Th1-reconstituted/pnir15.OVA-E. coli–colonized middle colon double-labeled with anti-CD3 (brown) and anti-BrdU (red). Arrowheads identify CD3+ DO11.RAG-2−/− T cells that have incorporated BrdU after 9 d in vivo administration. Note also the incorporation of BrdU by colonic crypt epithelial cells.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2196021&req=5

fig6: Histological analyses of colonic tissues from mice with Th1- or Th2-mediated colitis. Paraffin-embedded sections of colon from the indicated experimental groups were processed and stained as described in Materials and Methods. (A) Th1- and Th2-reconstituted/pnir15.OVA-E. coli-colonized, serial sections of proximal colon stained with anti-CD3 to identify T cells (left, top, and bottom) or Leder stain to identify neutrophils and eosinophils (right, top, and bottom). Arrows identify intraepithelial Th1 cells in diseased proximal colon. (B) Proximal colon from naive-reconstituted RAG-2−/− mice colonized with pnir15.TET-E. coli (top) or pnir15.OVA-E. coli mice (bottom) stained with anti-CD3. (C) Low and high power images of Th1-reconstituted/pnir15.OVA-E. coli–colonized middle colon double-labeled with anti-CD3 (brown) and anti-BrdU (red). Arrowheads identify CD3+ DO11.RAG-2−/− T cells that have incorporated BrdU after 9 d in vivo administration. Note also the incorporation of BrdU by colonic crypt epithelial cells.
Mentions: The histologic features of disease in Th1 and Th2 recipient mice colonized with pnir15.OVA-E. coli were distinct. The lesions in mice that received Th1 cells were characterized by predominantly mononuclear cell infiltrates composed of lymphocytes and monocytes/macrophages that expanded the LP and distorted the crypt architecture (Fig. 6 and Table II). Focally, there was extension of the inflammation into the underlying muscularis and serosa. Scattered, small granulomas were evident, but were not a dominant feature. Frequent crypt abscesses were evident, and T cells invaded the epithelium. Neutrophils were present in the areas of most severe epithelial injury, particularly bordering and infiltrating damaged crypts. Eosinophils were rarely seen.

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