New classification of CD4+CD8a+ double positive cells in Crohn’s disease patients

Abstract

Abstract The gastrointestinal tract absorbs nutrition while providing a defense response to foreign antigens including enteric bacteria or food. Once the antigen enter the intestine, inflammatory mononuclear cells are accumulated quickly, however some tissue resident T cells, such as regulatory T cells (Tregs) block the excessive tissue damage. We previously demonstrated that mouse CD4+CD8a+ double expressing (DP)cells and Tregs complementary play an immuno-suppressive role in IE and LP, and a part of IE DP cells is originally developed from Tregs in LP. However, DP cells are not well characterized in human especially in inflammatory bowel disease (IBD) patients. We obtained human small intestinal tissue from 9 colon cancer patients as normal tissue, and 5 Crohn’s disease(CD) patients, dividing into inflamed and non-inflamed lesion, and analysed by Flow cytometry. We confirmed DP cells are located in both IE and LP in human. First, we demonstrated the ratio of DP cells in normal tissue was as same as in non-inflamed lesion of CD patients. As we expected, the ratio of DP cells in inflamed tissue of CD patients was significantly decreased compared to normal tissue and non-inflamed lesion of CD. Then, we analysed the surface marker of Human DP cells. Surface staining of CD27 and CD45RA showed distinct difference between DP cells and the other CD4 T cells. DP cells expressed more memory T cell marker (CD27−CD45RA−) and less effector T cell marker (CD27+CD45RA−) than the other CD4 subset. Futher more, the more fraction of IE DP cells expressed CD103 than LP DP cells. Conclusively, these data indicated that human DP cell reside both in IE and LP and that DP cells are not a single characterized population, and the DP cells were decreased in inflamed lesion in CD.