Thymic innate-like T cells shape CD8 tolerance via T-to-T antigen presentation, talk finds

An expert lecture on ImmuneZoom described how thymic innate-like T cells, including NKT cells, reside long-term in the thymus and express inflammatory mediators such as IFN-gamma, forming a reservoir of inflammation-associated self-antigens. Experiments with GFP/IFN-gamma model antigen, Jedi TCR transgenic mice and thymic organoids showed these cells induce negative selection of CD8 T cells through direct T-to-T antigen presentation across roughly a 700-fold affinity range; as few as 0.1–0.55% of thymic innate-like T cells efficiently eliminate self-reactive CD8 T cells. Unpublished work identified V-delta-7 TCR recognition of the IL-17 receptor A chain as a ligand driving gamma-delta T cell selection.