Administration of mAb against α(E)β7 prevents and ameliorates immunization-induced colitis in IL-2(-/-) mice

Björn R. Lúdvíksson*, Warren Strober, Ryuta Nishikomori, Syed K. Hasan, Rolf O. Ehrhardt

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

72 Citations (Scopus)


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 α(E)β7 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 α(E)β7 in colitis, we administered a mAb against α(E)β7 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-γ production by lamina propria lymphocytes isolated from IL-2(-/-) TNP-OVA-immunized mice treated with anti-α(E)β7 was significantly lower than in untreated IL-2(-/-) TNP- OVA-immunized mice. In contrast, IFN-γ 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 α(E)β7 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 α(E)β7.

Original languageEnglish
Pages (from-to)4975-4982
Number of pages8
JournalJournal of Immunology
Issue number8
Publication statusPublished - 15 Apr 1999


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