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CD18 Is Required for Intestinal T Cell Responses at Multiple Immune Checkpoints¹

Section of Gastroenterology, Department of Medicine, University of Chicago, Chicago, IL 60637

The intestinal immune response to oral Ags involves a complex multistep process. The requirements for optimal intestinal T cell responses in this process are unclear. LFA-1 plays a critical role in peripheral T cell trafficking and activation, however, its role in intestinal immune responses has not been precisely defined. To dissect the role of LFA-1 in intestinal immune responses, we used a system that allows for segregation of T cell migration and activation through the adoptive transfer of LFA-1-deficient (CD18^–/–) CD4⁺ T cells from DO11.10 TCR transgenic mice into wild-type BALB/c mice. We find that wild-type mice adoptively transferred with CD18^–/– DO11.10 CD4⁺ T cells demonstrate decreases in the numbers of Ag-specific T cells in the intestinal lamina propria after oral Ag administration. We also find that in addition to its role in trafficking to intestinal secondary lymphoid organs, LFA-1 is required for optimal CD4⁺ T cell proliferation in vivo upon oral Ag immunization. Furthermore, CD18^–/– DO11.10 CD4⁺ T cells primed in the intestinal secondary lymphoid organs demonstrate defects in up-regulation of the intestinal-specific trafficking molecules, ₄₇ and CCR9. Interestingly, the defect in trafficking of CD18^–/– DO11.10 CD4⁺ T cells to the intestinal lamina propria persists even under conditions of equivalent activation and intestinal-tropic differentiation, implicating a role for CD18 in the trafficking of activated T cells into intestinal tissues independent of the earlier defects in the intestinal immune response. This argues for a complex role for CD18 in the early priming checkpoints and ultimately in the trafficking of T cells to the intestinal tissues during an intestinal immune response.

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¹ This work was supported by the Crohn’s and Colitis Foundation of America, National Institutes of Health Grant DK02905 (to C.A.), and University of Chicago Digestive Disease Center Grant DK42086.

² Address correspondence and reprint requests to Dr. Clara Abraham, Department of Medicine, University of Chicago, 5841 South Maryland Avenue, MC 6084, Chicago, IL 60637. E-mail address: cabraham{at}medicine.bsd.uchicago.edu

³ Abbreviations used in this paper: MLN, mesenteric lymph nodes; WT, wild type; DO11.10 mice, OVA-specific TCR-transgenic mice; PP, Peyer’s patches; PLN, peripheral lymph nodes; LPL, lamina propria lymphocytes; DC, dendritic cells; CTO, cell tracker orange; LB, large bowel; SB, small bowel.

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