Spontaneous Inflammatory Bowel Disease in Multiple Mutant Mouse Lines: Association with Colonization by <i>Helicobacter hepaticus</i>

Foltz, Calvin M.; Fox, James G.; R, Cahill; Murphy, James C.; Yan, Lili; Shames, B; Schauer, David B.

doi:10.1046/j.1523-5378.1998.08006.x

Cited by 106 publications

(93 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Rather, they likely differentiated into T CM after reacting against allergens or commensual and pathogenic organisms that can infect laboratory mice (37)(38)(39)(40)(41)(42). Alternatively, these T CM phenotype cells could be the product of lymphopenia-induced proliferation, which occurs early in the development of the immune system (43)(44)(45)(46).…”

Section: Discussionmentioning

confidence: 99%

Central Memory CD8+ T Cells Induce Graft-versus-Host Disease and Mediate Graft-versus-Leukemia

Zheng

Matte-Martone

Jain³

et al. 2009

The Journal of Immunology

109

View full text Add to dashboard Cite

In allogeneic hemopoietic stem cell transplantation, mature donor ␣␤ T cells in the allograft promote T cell reconstitution in the recipient and mediate the graft-vs-leukemia (GVL) effect. Unfortunately, donor T cells can attack nonmalignant host tissues and cause graft-vs-host disease (GVHD). It has previously been shown that effector memory T cells not primed to alloantigen do not cause GVHD yet transfer functional T cell memory and mediate GVL. Recently, central memory T cells (T CM ) have also been reported to not cause GVHD. In contrast, in this study, we demonstrate that purified CD8؉ T CM not specifically primed to alloantigens mediate GVHD in the MHC-mismatched C57BL/6 (B6)3 BALB/c and the MHC-matched, multiple minor histocompatibility Ag-mismatched C3H.SW3 B6 strain pairings. CD8؉ T CM and naive T cells (T N ) caused similar histological disease in liver, skin, and bowel. B6 CD8؉ T CM and T N similarly expanded in BALB/c recipients, and the majority of their progeny produced IFN-␥ upon restimulation. However, in both models, CD8؉ T CM induced milder clinical GVHD than did CD8 ؉ T N . Nonetheless, CD8 ؉ T CM and T N were similarly potent mediators of GVL against a mouse model of chronic-phase chronic myelogenous leukemia. Thus, in contrast to what was previously thought, CD8؉ T CM are capable of inducing GVHD and are substantially different from T EM but only subtly so from T N .

show abstract

Section: Discussionmentioning

confidence: 99%

Central Memory CD8+ T Cells Induce Graft-versus-Host Disease and Mediate Graft-versus-Leukemia

Zheng

Matte-Martone

Jain³

et al. 2009

The Journal of Immunology

109

View full text Add to dashboard Cite

show abstract

“…We colonized Nod2-deficient mice with the opportunistic pathogen, Helicobacter hepaticus. H. hepaticus, a Gram-negative microaerophilic bacterium, is a common mouse intestinal commensal in most animal facilities in the United States and colonizes the intestinal crypts of the cecum and colon, establishing a life-long infection (30).…”

Section: Nod2 Suppresses De Novo Colonization Of Opportunistic Pathogmentioning

confidence: 99%

Nod2 is required for the regulation of commensal microbiota in the intestine

Petnicki‐Ocwieja

Hrncírová

Liu

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

509

450

View full text Add to dashboard Cite

Mutations in the Nod2 gene are among the strongest genetic risk factors in the pathogenesis of ileal Crohn's disease, but the exact contributions of Nod2 to intestinal mucosal homeostasis are not understood. Here we show that Nod2 plays an essential role in controlling commensal bacterial flora in the intestine. Analysis of intestinal bacteria from the terminal ilea of Nod2-deficient mice showed that they harbor an increased load of commensal resident bacteria. Furthermore, Nod2-deficient mice had a diminished ability to prevent intestinal colonization of pathogenic bacteria. In vitro, intestinal crypts isolated from terminal ilea of Nod2-deficient mice were unable to kill bacteria effectively, suggesting an important role of Nod2 signaling in crypt function. Interestingly, the expression of Nod2 is dependent on the presence of commensal bacteria, because mice re-derived into germ-free conditions expressed significantly less Nod2 in their terminal ilea, and complementation of commensal bacteria into germ-free mice induced Nod2 expression. Therefore, Nod2 and intestinal commensal bacterial flora maintain a balance by regulating each other through a feedback mechanism. Dysfunction of Nod2 results in a break-down of this homeostasis.commensal bacteria ͉ Crohn's disease ͉ mouse ͉ NLR

show abstract

“…30 In the current study, three animals in one strain, strain 2, had a prolapsed rectum and were examined for entero-and typhlocolitis. Although severe inflammation was apparent in the prolapsed tissue, the remainder of the gastrointestinal tract contained only mild or no inflammation.…”

Section: Pathologymentioning

confidence: 99%

Differential Susceptibility to Hepatic Inflammation and Proliferation in AXB Recombinant Inbred Mice Chronically Infected with Helicobacter hepaticus

Ihrig

Schrenzel

Fox

1999

The American Journal of Pathology

Self Cite

View full text Add to dashboard Cite

Helicobacter hepaticus is a naturally occurring pathogen of mice and has been used to develop models of chronic hepatitis , liver cancer , and , more recently , inflammatory bowel disease , in selected mouse strains. A/JCr mice are particularly susceptible to H. hepaticus-induced hepatitis and subsequent development of liver neoplasms , whereas C57BL/6 mice are resistant. In this study , we inoculated nine AXB recombinant inbred (RI) mouse strains , derived from A/J and C57BL/6 mice , with H. hepaticus to determine the genetic basis of resistance to Helicobacterinduced liver disease. Mice were surveyed 14 months after inoculation by culture and PCR for H. hepaticus colonization of the liver and cecum , and microscopic morphometric evaluations of the liver were performed to quantify and correlate the severity of inflammation , apoptosis , and proliferation. Analysis of variance of hepatic inflammation demonstrated significant variation among the RI strains (P < 0.0001), and the strain distribution pattern suggested a multigenic basis of disease resistance. Quantitative trait analysis using linear regression suggested possible linkage to loci on mouse chromosome 19. Hepatocellular and biliary epithelial apoptosis and proliferation indices , including proliferation of oval cells, were markedly increased and correlated with severity of inflammation. Prevalence of hepatic neoplasia was also increased in susceptible RI strains. These findings demonstrate a genetic basis for susceptibility to Helicobacter-induced disease and provide insight into its pathogenesis. (Am J Pathol 1999, 155:571-582)Helicobacter hepaticus is a well-described, naturally occurring pathogen of mice that causes chronic hepatitis and cancer and has been used as a model for the study of both hepatic carcinogenesis and the biology of Helicobacter-induced gastrointestinal disease. Like Helicobacter pylori, the organism is a gram-negative, ureasepositive, helical bacterium that is transmitted through fecal-oral contamination and results in chronic immune cell stimulation, inflammation, and neoplasia in susceptible animals.1-3 In A/J mice, infection causes severe hepatitis and the eventual development of preneoplastic altered foci, hyperplasia, adenoma, and carcinoma in the liver. In contrast, C57BL/6 mice infected with H. hepaticus are highly resistant to the development of disease and have minimal or no liver lesions.2 As with H. pylori-induced gastritis in people, the particular host factors in A/J and C57BL/6 mice that alter the pathogenesis and severity of disease expression after infection with H. hepaticus are poorly understood. Several studies have implicated an imbalance or dysregulation in immunity in response to the bacteria similar to that seen in H. pylori gastritis. [3][4][5][6]

show abstract

Spontaneous Inflammatory Bowel Disease in Multiple Mutant Mouse Lines: Association with Colonization by Helicobacter hepaticus

Cited by 106 publications

References 30 publications

Central Memory CD8+ T Cells Induce Graft-versus-Host Disease and Mediate Graft-versus-Leukemia

Central Memory CD8+ T Cells Induce Graft-versus-Host Disease and Mediate Graft-versus-Leukemia

Nod2 is required for the regulation of commensal microbiota in the intestine

Differential Susceptibility to Hepatic Inflammation and Proliferation in AXB Recombinant Inbred Mice Chronically Infected with Helicobacter hepaticus

Contact Info

Product

Resources

About