CD18 Is Required for Intestinal T Cell Responses at Multiple Immune Checkpoints
| Autor: | Marissa Marski, Alice L. Ye, Clara Abraham |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
CD4-Positive T-Lymphocytes
Adoptive cell transfer Integrin alpha4 T cell Immunology CCR9 Priming (immunology) CD18 Biology Lymphocyte Activation Mice Receptors CCR Interleukin 21 Immune system Cell Movement medicine Animals Immunology and Allergy Antigens Intestinal Mucosa Immunity Mucosal Cell Proliferation Mice Knockout Mice Inbred BALB C Lymphocyte Function-Associated Antigen-1 Up-Regulation Cell biology medicine.anatomical_structure CD18 Antigens T cell migration Immunization Receptors Chemokine |
| Zdroj: | The Journal of Immunology. 178:2104-2112 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | 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, α4β7 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. |
| Databáze: | OpenAIRE |
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