CD8+ Cytotoxic T Cells Induce Relapsing Colitis in Normal Mice

Nancey, Stéphane; Holvoet, Sébastien; Graber, I. G.; Joubert, Grégoire; Philippe, David; Martin, Stefan F.; Nicolas, Jean‐François; Desreumaux, Pierre; Flourié, Bernard; Kaiserlian, Dominique

doi:10.1053/j.gastro.2006.05.018

Cited by 95 publications

(109 citation statements)

References 40 publications

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“…Mice were anesthetized using ketamine-xylazine and DNBS-specific colonic DTH was induced as previously described (13). Briefly, mice immunized by an intrarectal enema of 80 mg/kg of DNBS diluted in 50% ethanol (v/v) were challenged 5 days later with 40 mg/kg DNBS (unless otherwise stated).…”

Section: Dnbs-specific Colonic Dth-mediated Colitismentioning

confidence: 99%

“…The frequency of hapten-specific IFN-␥-producing T cells was determined as described elsewhere (13). The number of IFN-␥ spot-forming cells (SFC) was counted and the results are expressed as the number of IFN-␥ SFC per 10 6 cells.…”

Section: Ifn-␥ Elispotmentioning

confidence: 99%

“…Colon fragments were incubated with 5 mM EDTA in PBS to remove epithelial cells and LP leukocytes were extracted from the remaining tissue by a 45-min incubation at 37°C in 35 g/ml Liberase (Roche Diagnostics) and 10 U/ml DNase (Roche Diagnostics) as previously described (13). Leukocytes were enriched by centrifugation over 40% Percoll (GE Healthcare).…”

Section: Isolation Of Colon Lp Leukocytesmentioning

confidence: 99%

“…However, the inefficacy of anti-CD4 mAb therapy in patients with IBD (12) may be explained by the colitogenic function of T cells being distinct from CD4 ϩ T cells and/or elimination of regulatory CD4 ϩ T cells. The unanticipated role of CD8 ϩ T cells in IBD (13,14) and autoimmune enteropathy (15)(16)(17) is now emerging from studies using normal or TCR-transgenic immunocompetent mice as well as studies using SAMP1/Yit mutant or TNF ⌬ARE mice (18,19). These studies revealed that intestinal inflammation can be initiated by MHC class I-restricted CD8 ϩ T cells in response to self or exogenous Ags present in the intestinal mucosa.…”

mentioning

confidence: 99%

“…These studies revealed that intestinal inflammation can be initiated by MHC class I-restricted CD8 ϩ T cells in response to self or exogenous Ags present in the intestinal mucosa. In particular, we documented in BALB/c mice that acute colitis and its relapsing episodes result from an Ag-specific colonic delayed-type hypersensitivity (DTH) reaction that is initiated by CD8 ϩ T cells without need for CD4 ϩ T cell help (13). In this model, 2,4-dinitrobenzene sulfonic acid (DNBS)-specific IFN-␥-producing CD8 ϩ T cells were generated in BALB/c mice by intracolonic DNBS immunization.…”

mentioning

confidence: 99%

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CD4+ T Cells and Lactobacillus casei Control Relapsing Colitis Mediated by CD8+ T Cells

Hacini‐Rachinel

Nancey²,

Boschetti³

et al. 2009

The Journal of Immunology

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Evidence that CD4+ regulatory T cells can control Ag-specific CD8+ T cell-mediated colitis in immunocompetent mice is poorly documented. To examine the potential of CD4+ T cells to control colitis, we used our model of CD8+ T cell-mediated colitis induced by intracolonic sensitization followed by challenge with the hapten 2,4-dinitrobenzene sulfonic acid. The defect of CD4+ T cells in MHC class II-deficient (Aβ°/°) mice allowed priming of 2,4-dinitrobenzene sulfonic acid-specific IFN-γ-producing CD8 colitogenic effectors and development of colitis in the otherwise resistant C57BL/6 strain. Cotransfer experiments in RAG2°/° mice and ex vivo studies showed that CD4+CD25+ T cells completely prevented CD8+ T cell-mediated colitis and controlled CD8+ T cell activation, respectively. In the susceptible BALB/c strain, Ab depletion revealed that lack of CD4+ regulatory T cells resulted in 1) acute colitis elicited by a suboptimal dose of hapten challenge and 2) more severe relapsing episodes of colitis induced by effector/memory CD8+ T cell-mediated colitis at an optimal dose of hapten challenge, even when CD4 depletion was performed just before the second challenge. Oral administration of the probiotic strain Lactobacillus casei DN-114 001 alleviated colitis and increased the suppressive function of Foxp3+CD4+ regulatory T cells of colon lamina propria. These data demonstrate that CD4+ regulatory T cells exert a protective effect on colitis by controlling colitogenic effector/memory CD8+ T cells during the effector (symptomatic) phase of acute and relapsing colitis, respectively. Probiotics with natural adjuvant effects on mucosal regulatory T cells may represent a valuable approach to alleviate the colitogenic effect of Tc1-type CD8+ effectors.

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Section: Dnbs-specific Colonic Dth-mediated Colitismentioning

confidence: 99%

Section: Ifn-␥ Elispotmentioning

confidence: 99%

Section: Isolation Of Colon Lp Leukocytesmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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CD4+ T Cells and Lactobacillus casei Control Relapsing Colitis Mediated by CD8+ T Cells

Hacini‐Rachinel

Nancey²,

Boschetti³

et al. 2009

The Journal of Immunology

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Pequi Oil, a MUFA/Carotenoid‐Rich Oil, Exhibited Protective Effects against DSS‐Induced Ulcerative Colitis in Mice

Moreno

Evangelista‐Silva

Santos

et al. 2021

Euro J Lipid Sci & Tech

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Inflammatory bowel diseases (IBD) affect the gastrointestinal tract, and the imbalance of intestinal immune homeostasis can trigger them. Pequi oil (PO), a monounsaturated (MUFA) and carotenoid-rich food with nutraceutical potential, could help reshape the intestinal immune response, ameliorating IBD outcomes. This study investigates the effects of a 28 days intake of PO on elements of the intestinal immune response of mice with DSS-induced ulcerative colitis (disease activity index, colonic damage, inflammatory cells and markers). PO reduces body weight, colonic crypt and goblet cell losses and ameliorates diarrhea. In the colon, it increases T cells and secretory-IgA and decreases CD8+T cells. In lymphoid organs, it reduces CD8+T cells. Moreover, it also reduces the IL-17 and CRP in plasma. PO oil promotes a less cytotoxic response that may protect mice from immunological injuries caused by an IBD in the intestinal mucosa, improving the disease prognosis. Practical applications: This study demonstrates that the intake of pequi oil contributes to the regulation of immune response and improves clinical and histological signs of DSS-induced ulcerative colitis in mice. Its effects in cytotoxic cell reduction and other inflammatory markers and stimulation of regulatory cells, and preservation of mucus-producing cells, provide news insights about the importance of the regular intake of this food to better prognosis of ulcerative colitis acute episodes. In addition, these findings encourage further studies with foods with a protective potential for the intestinal mucosa.

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Genetics of the innate immune response in inflammatory bowel disease

Limbergen

Russell

Nimmo

et al. 2007

Inflammatory Bowel Diseases

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The discovery of nucleotide-binding oligomerization domain 2/caspase recruitment domain-containing protein 15 (NOD2/CARD15) as the first susceptibility gene in Crohn's disease (CD) has shifted the focus of research into the pathogenesis of inflammatory bowel disease (IBD) firmly to the innate immune response and the integrity of the epithelial barrier. The subsequent implication in IBD of variant alleles of OCTN, DLG5, MDR1, and TLRs has provided further support for a new, more complex model of innate immunity function in the gastrointestinal tract. In this review, we examine the recent advances in our understanding of the influence of genetics of the innate immune response on IBD. We will focus on germline variation of genes encoding pathogen-recognition receptors, proteins involved in epithelial homeostasis and secreted antimicrobial proteins.

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CD8+ Cytotoxic T Cells Induce Relapsing Colitis in Normal Mice

Cited by 95 publications

References 40 publications

CD4+ T Cells and Lactobacillus casei Control Relapsing Colitis Mediated by CD8+ T Cells

CD4+ T Cells and Lactobacillus casei Control Relapsing Colitis Mediated by CD8+ T Cells

Pequi Oil, a MUFA/Carotenoid‐Rich Oil, Exhibited Protective Effects against DSS‐Induced Ulcerative Colitis in Mice

Genetics of the innate immune response in inflammatory bowel disease

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