Administration of mAb against alpha E beta 7 prevents and ameliorates immunization-induced colitis in IL-2-/- mice.

Abstract

We previously demonstrated that 2,4,6-trinitrophenol (TNP)-OVA immunization leads to a transmural colitis in the IL-2-/- mouse that is caused by IL-12-driven CD4+ Th1 T cells and resembles human Crohn's disease. The integrin alpha E beta 7 is highly expressed on colonic intraepithelial lymphocytes and has been suggested to function as a homing or retention molecule for intraepithelial lymphocytes. To evaluate the role of alpha E beta 7 in colitis, we administered a mAb against alpha E beta 7 to IL-2-/- mice that were immunized at the same time with TNP-OVA in CFA. To our surprise, this treatment resulted in a significantly reduced colitis severity score, 0-2 vs 3-4, that was associated with a significant reduction in CD4+ lamina propria lymphocyte subpopulation (p < 0.01). In contrast, the total number of splenic CD4+ T cells of treated animals was significantly elevated compared with that of untreated animals (3.2 +/- 0.6 x 107 vs 1.2 +/- 0.2 x 107; p < 0.05). Similarly, functional studies revealed that IFN-gamma production by lamina propria lymphocytes isolated from IL-2-/- TNP-OVA-immunized mice treated with anti-alpha E beta 7 was significantly lower than in untreated IL-2-/- TNP-OVA-immunized mice. In contrast, IFN-gamma production by splenic cells isolated from treated IL-2-/- TNP-OVA-immunized mice was significantly higher than in untreated mice. Finally, TNP-OVA-immunized IL-2-/- mice that were treated after the colitis had been established also showed a significant decrease in mucosal inflammation after alpha E beta 7 mAb administration. Thus, the above findings demonstrate that the onset and maintenance of inflammatory bowel disease depends on the colonic localization of lamina propria CD4+ lymphocytes expressing alpha E beta 7.

• Authors: B R Lúdvíksson, W Strober, R Nishikomori, S K Hasan, R O Ehrhardt
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 162 Issue 8 Pg. 4975-82 (Apr 15 1999) ISSN: 0022-1767 [Print] United States
• PMID: 10202045 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• CD3 Complex
• Haptens
• Integrins
• Interleukin-2
• Trinitrobenzenes
• integrin alphaEbeta7
• trinitrophenyl-ovalbumin
• Intercellular Adhesion Molecule-1
• Interferon-gamma
• Ovalbumin

Topics

• Animals
• Antibodies, Monoclonal (administration & dosage, therapeutic use)
• CD3 Complex (analysis)
• CD4 Lymphocyte Count
• Cell Movement (genetics, immunology)
• Colitis (genetics, immunology, pathology, prevention & control)
• Female
• Haptens (immunology)
• Immunization
• Injections, Intraperitoneal
• Integrins (immunology)
• Intercellular Adhesion Molecule-1 (analysis)
• Interferon-gamma (biosynthesis)
• Interleukin-2 (genetics)
• Intestinal Mucosa (pathology)
• Lymphocyte Count
• Lymphocytes (metabolism, pathology)
• Male
• Mice
• Mice, Knockout
• Ovalbumin (immunology)
• Spleen (cytology, metabolism)
• Trinitrobenzenes (immunology)