Unconventional T cells, including TCR γδ cells, natural killer T(NKT) cells, and mucosa-associated invariant T(MAIT) cells, have emerged as critical players in the pathogenesis of inflammatory bowel disease(IBD), contributing to the chronic inflammation as seen in the gut through dysregulated immune responses and tissue damage. Immuno-regulatory molecules belonging to butyrophilin(BTN) family may modulate T cell function by interacting with one chain of the TCR. Whether BTN molecules affect MR1-restricted T cells remains to be investigated.
MR1T cells are a novel type of T cells that show a high degree of TCR αβ diversity and are autoreactive towards MR1. They can recognize MR1-expressing tumor cells as well as modulate MUC2 gene expression by intestinal epithelial cell lines. However, the role of MR1T cells and the influence of immune regulatory molecules such as BTN family members on IBD pathogenesis is not known.
This study investigated the presence of MR1-restricted T cells and their antigen specificities by expanding cells from the gut biopsies of patients with ulcerative colitis and staining them with MR1 tetramers loaded with different antigens. Moreover, we also studied the influence of butyrophilin-like 3(BTNL3) and butyrophilin-like 8(BTNL8) on MR1-restricted TCR γδ cells expressing the Vγ4 chain. We generated cells transduced with the MR1 gene, or with BTNL3 and BTNL8 genes or with all three genes. The transfectants have been selected and are being used to generate T cell clones restricted to MR1 and expressing the TCR Vγ4 chain. These different antigen-presenting cells will be then used to investigate the effects of BTNL molecules on the capacity of T cells to release cytokines, proliferate and kill target cells expressing or not BTNL proteins. Together, these studies may provide valuable and novel insights into the complex interplay between T-cell responses in the gut and the pathogenesis of IBD.