Induction and prevention of colonic inflammation in IL-2-deficient mice.

Abstract

Gene-targeted mice deficient for IL-2 (IL-2 -/- mice) are free of apparent disease when maintained under germfree conditions but develop colitis and autoimmunity in a conventional environment. Here we show that colitis can be reproducibly induced in IL-2 -/- mice, but not in IL-2 +/+ mice, by i.p. immunization with Ag in CFA; thus enabling the systematic study of the immunopathogenesis of the colitis. We found that TNP-KLH or TNP-OVA had the most significant effect in inducing colitis, and while TNP-KLH immunization leads to the early appearance of activated T cells in the colons of both IL-2 -/- and IL-2 +/+ mice, only lamina propria cells of IL-2 -/- mice produced high amounts of INF-gamma. Moreover, both infiltrating colon CD4+ (69%) and CD8+ (6%) T cells secrete large amounts of IFN-gamma; however, only the depletion of CD4+ T cells leads to abrogation of the inflammation. In further analysis, we showed that the high IFN-gamma production is IL-12 driven, since colonic tissues of IL-2 -/- mice but not IL-2 +/+ mice show the presence of heterodimeric IL-12 and co-administration of anti-IL-12 with TNP-KLH completely prevented colitis and significantly reduced IFN-gamma production. Finally, we demonstrate that IL-2 -/- mice are deficient in their ability to induce Th2 responses after TNP-KLH challenge and that such immunization also leads to autoimmune-like phenomena in other organs of IL-2 -/- mice. These findings suggest that in the absence of IL-2 systemic administration of Ag induces primarily Th1 cells driven by overexpression of heterodimeric IL-12.

Comparison of microbial communities and the profile of sulfate-reducing bacteria in patients with ulcerative colitis and their association with bowel diseases: a pilot study

“…Indirect evidence for the interaction between the luminal microbiota and the immune system exists from studies using animal models with disruptions in immunoregulatory molecules. It was reported that spontaneous colitis, which consistently develops in knockout and transgenic murine models, does not occur when these mice are maintained in germ-free conditions [ 53 – 56 ]. Furthermore, it should be noted that only two genera of the Desulfovibrionaceae family ( Desulfovibrio and a taurine-respiring sulfite-reducing Bilophila ) were detected in the feces of the various patients before and after cultivation in the SRB medium.…”

Partial Protection against Dextran Sodium Sulphate Induced Colitis in Histamine‐Deficient, Histidine Decarboxylase Knockout Mice

“…The various experimental models have in common a dependence on the presence of normal nonpathogenic bacterial flora. In fact, none of the mouse models of mucosal inflammation develop inflammation under germ‐free conditions, including IL‐10 −/− mice (18), TCRα −/− mice (19,20), IL‐2 −/− (21) mice, and SAMP1/Yit mice (22).…”

Atividade imunomoduladora da alga Chlorella vulgaris em camundongos portadores de tumos ascitico de Ehrlich

“…Vários estudos demonstram que a citocina IL-2, sozinha ou em combinação com IFNs, também aumenta a atividade lítica de células NK (Kuribayashi et al 1981;Hefeneider et al 1983;Henney et al 1981;Misawa et al 2000;Sayers et al 1989;Young et al 1987), as quais produzem e secretam uma variedade de moléculas imunoreguladoras que atuam sinergicamente com IFNs, com a própria IL-2, ou com citocinas induzidas por IL-2, para ativação de respostas antitumorais (Allavena et al 1985;Svedersky et al 1985). A IL-2 foi inicialmente identificada como fator de crescimento de células T (Ehrhardt et al 1997;Taniguchi et al 1983).…”