CD18 is required for intestinal T cell responses at multiple immune checkpoints.
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, alpha(4)beta(7) 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.
Marski
Marissa
M
Section of Gastroenterology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
Ye
Alice L
AL
Abraham
Clara
C
D000818:Animals; D000941:Antigens / Q000276:immunology / Q000494:pharmacology; D018821:CD18 Antigens / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D049109:Cell Proliferation; D018928:Immunity, Mucosal / Q000235:genetics; D007114:Immunization; D039441:Integrin alpha4 / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D054388:Receptors, CCR; D019707:Receptors, Chemokine / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D000941:Antigens; C119309:CC chemokine receptor 9; D018821:CD18 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D054388:Receptors, CCR; D019707:Receptors, Chemokine; D039441:Integrin alpha4