Consequences of Fas-ligand and perforin expression by colon T cells in a mouse model of inflammatory bowel disease

Simpson, Stephen J.; Jong, Ype P. de; Shah, Samir A.; Comiskey, Martina; Wang, Baoping; Spielman, Julie; Podack, E R; Mizoguchi, Emiko; Bhan, Atul K.; Terhorst, Cox

doi:10.1016/s0016-5085(98)70256-2

Cited by 23 publications

(13 citation statements)

References 37 publications

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“…Therefore, IL-4 secreted by activated colonic TCR +ˇ+ cells may lead to the deterioration of colitis. Additionally, as colitis in tg 4 26 mice reconstituted using perforin-deficient colonic T cells is milder than that using wild-type colonic T cells [29], perforin-mediated cytotoxicity of colonic TCR +ˇ+ cells may also enhance the destruction of colonic architecture in TCR § -/-mice.…”

Section: Discussionmentioning

confidence: 99%

An accessory role of TCRγ δ+ cells in the exacerbation of inflammatory bowel disease in TCRα mutant mice

et al. 2001

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T cell receptor α mutant (TCRα –/–) mice, which spontaneously develop colitis under conventional conditions, did not show any signs of colitis under germ‐free conditions, leaving TCRα –β + cells (β dim cells) and TCRγ δ + cells much reduced. Moreover, TCRα –/– mice with alymphoplastic mutation (aly/aly TCRα –/– mice), which lack Peyer's patches and peripheral lymph nodes, did not suffer from colitis. While both β dim cells and TCRγ δ + cells were present in the colons of aly/aly TCRα –/– mice and aly/+ TCRα –/– mice, cytotoxicity of colonic TCRγ δ + cells in aly/aly TCRα –/– mice was almost abolished. Transfer of TCRγ δ + cells from TCRα –/– mice into scid/scid mice or aly/aly TCRα –/– mice could not induce colitis, but injection of anti‐TCRδ mAb into TCRα –/– mice prevented colitis from developing. Finally, TCRα –/– mice expressing transgenic (Tg) KN6‐TCRγ δ hardly developed colitis, accompanied by colonization of non‐cytotoxic Tg TCRγ δ + cells in their colonic mucosa. These results demonstrate that intestinal resident TCRγ δ + cells may be involved in the exacerbation of inflammatory bowel disease in TCRα –/– mice.

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Section: Discussionmentioning

confidence: 99%

An accessory role of TCRγ δ+ cells in the exacerbation of inflammatory bowel disease in TCRα mutant mice

et al. 2001

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“…Several cytotoxic systems exist in T cells that might participate in tissue destruction. As mentioned above, LP CD4+ T cells express FasL and kill Fas-expressing targets ex vivo [63,65]. Colonic ECs have been shown to express Fas [85] and to be susceptible to apoptosis induced by Fas cross-linking in vitro [86], hence a possible role for the Fas-FasL system has been suggested in the destruction of the epithelial barrier observed in IBD [86].…”

Section: What Mediates Tissue Destruction In Ibd?mentioning

confidence: 96%

“…This idea is supported by the fact that the apoptotic cells are derived from the pool of activated, proliferating cells [15]. The pathogenic significance of apoptosis is unknown, but disease severity remained unchanged when IBD was induced by the transfer of bone marrow from FasL-KO mice into tgÂ26 mice [65], thus throwing into question a direct role for Fas-mediated apoptosis in the pathogenesis of IBD, although not excluding the significance of apoptosis in the pathogenesis of chronic inflammation.…”

Section: Activation Turnover and Recruitment Of Lp Cd4+ T Cells In Ibdmentioning

confidence: 99%

“…This idea is supported by the presence of extensive crypt degeneration and cell death in the colonic epithelium in CD4+ T-cell-transplanted SCID mice [14]. However, this hypothesis is called into question by the fact that FasL-KO cells induce the same intestinal pathology as WT cells in bone-marrow-transplanted tgÂ26 mice [65], and by the inability of freshly isolated colonic T cells from IL-2KO mice to kill syngeneic colon ECs ex vivo [87].…”

Section: What Mediates Tissue Destruction In Ibd?mentioning

confidence: 99%

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Cells and Cytokines in the Pathogenesis of Inflammatory Bowel Disease: New Insights from Mouse T Cell Transfer Models

Bregenholt

2000

Exp Clin Immunogenet

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Recently, a number of experimental models of human inflammatory bowel disease (IBD) of immunological basis have been developed. These have proven useful tools in the study of IBD, allowing a more detailed dissection of the pathogenesis of the disease. Studies from these models have revealed new, important knowledge about environmental factors, cell subset, cytokines and effector molecules in the pathogenesis of IBD. This review focuses on recent advances in the understanding of the development of IBD obtained from adoptive CD4+ T cell transfer models of the disease.

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“…54 CD95-dependent cytotoxic activity in vitro was shown using lamina propria cells from mice in which colitis was induced by transfer of wildtype (WT) bone marrow (BM) into T-cell and natural killer cell-deficient mice. 55 In this model, however, colitis also developed when BM cells from gld (expressing nonfunctional CD95L) instead of WT mice were transferred, whereas colitis was less severe after transferring cells with defects in another cytotoxic molecule, perforin. These results suggest that expression of CD95L is not the only way by which cytotoxic T-lymphocytes kill target cells.…”

Section: Cd95 In Uc: Yesterday and Todaymentioning

confidence: 90%

Cell death in the colonic epithelium during inflammatory bowel diseases

Chen¹,

Park²,

Turner³

et al. 2010

Inflammatory Bowel Diseases

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CD95 is a member of the death receptor family. It is a prototypical inducer of apoptosis that, upon binding of its cognate ligand (CD95L), forms a death-inducing signaling complex composed of adaptor molecules and initiator caspases that transmit the apoptosis signal. The CD95/CD95L system was implicated in the etiology of inflammatory bowel disease (IBD) based, primarily, on the finding that CD95 is highly expressed in the intestinal epithelial cells and that epithelial apoptosis is increased in IBD. In recent years it has been recognized that CD95, while playing an important role as an apoptosis-inducing receptor in the immune system, also has multiple nonapoptotic functions on nonimmune cells. This review critically discusses the data on the possible function of CD95 as an apoptosis-inducing receptor in IBD and discusses alternative mechanisms for epithelial cell loss in IBD.

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Consequences of Fas-ligand and perforin expression by colon T cells in a mouse model of inflammatory bowel disease

Cited by 23 publications

References 37 publications

An accessory role of TCRγ δ+ cells in the exacerbation of inflammatory bowel disease in TCRα mutant mice

An accessory role of TCRγ δ+ cells in the exacerbation of inflammatory bowel disease in TCRα mutant mice

Cells and Cytokines in the Pathogenesis of Inflammatory Bowel Disease: New Insights from Mouse T Cell Transfer Models

Cell death in the colonic epithelium during inflammatory bowel diseases

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