Poster Presentation CD1-MR1 2024

Development of a novel assay to examine the cross-talk between regulatory T cells and MAIT cells (#208)

Amanda Ho 1 2 , Fei Han 1 2 , Chuyao Chen 2 , Dan He 1 2 , Yiting Xue 1 2 , Huizhong Xu 1 2 , Zhengyu Wu 2 , Xingchi Chen 2 , Laura Cook 3 , Edwin Leeansyah 1 2
  1. Precision Medicine and Healthcare Research Centre, Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen, Guangdong, China
  2. Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, Guangdong, China
  3. Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia

Mucosa-associated invariant T (MAIT) cells are a subpopulation of unconventional T cells that exert potent antibacterial responses when activated in an MHC class Ib protein (MR1)-dependent manner. The production of effector cytokines such as interferon gamma (IFNγ), tumour necrosis factor (TNF) and cytolytic proteins such as granzyme B (GrzB), induce effective lysis and elimination of infected cells. Conversely, maintenance of self-tolerance and response towards excessive inflammation are mediated by regulatory T cells (Treg) that express high levels of the IL-2 receptor-α subunit CD25. Treg cells dampen the effector responses and suppress proliferation of effector T cell populations through various mechanism, including the release of immunosuppressive cytokines, such as IL-10. The properties of Treg cells have garnered interest as a therapeutic target, however their modulations on MAIT cells have yet to be elucidated

Here, we report development of a novel assay to examine the mechanisms of Treg cell immunosuppression on MAIT cell activation. Treg cells and CD25neg effector T cell populations were either depleted from, or isolated and expanded from, peripheral blood mononuclear cells (PBMCs). Following activation with Escherichia coli, the MAIT cell population in Treg cell-depleted PBMCs had increased TNF production compared to those in total PBMCs. MAIT cells cocultured with supernatant from anti-CD3/CD28 bead-activated Treg cell cultures exhibited a decreased functional response with lower expression of GrzB, CD107a, and TNF, compared to MAIT cells cocultured with CD25neg effector T cell supernatant. Compared to CD25neg T effector cells, Treg cell culture supernatant had increased levels of IL-10, IL-4, and IL-13 cytokines that was sustained up to 72 hours after activation.

These data are the first step in uncovering the interplays between these two specialized T cell subsets and identifying novel approaches to modulate excessive MAIT cell function in the setting of intestinal chronic inflammatory diseases such as inflammatory bowel disease.