LCH is characterised by lesions containing CD1a⁺ and/or CD207⁺ histiocytes as well as inflammatory cells, including T and B cells. New treatment options are required for the large proportion of patients who remain unresponsive to current standards. Recently, our group has identified CD1a⁺ T cells in LCH lesions, although their significance remains unclear. One possibility is that these cells and the lesions themselves reflect a deregulated microenvironment. FOXP3⁺ regulatory T cells (Tregs) are present in high numbers in LCH lesions (suggestive of an immune-suppressive environment), but the frequency and importance of other T cells with regulatory functions, such as mucosal-associated invariant T (MAIT) cells, natural killer T (NKT) cells and gamma-delta (γδ) T cells is not known. This project represents the most comprehensive analysis of innate-like T cells in patients with LCH. We have analysed tissue samples from blood and lesions stored in the Fiona Elsey Cancer Research Institute’s Tissue Bank facility. Cells were characterized using 13-colour flow cytometry, and in vitro assays of T cell function. We have previously detected mature CD1a⁺ T cells in LCH lesions, but not in the peripheral blood of LCH patients or healthy donors and now report that there is a trend towards a decreased frequency of MAIT cells in the blood and lesions from LCH patients compared with healthy donors.  These findings suggest that immune regulation is defective in LCH and that changes in these T cell subsets may be important factors in LCH onset and progression. Targeting these factors could therefore be a promising avenue of investigation in the development of new immune based therapies.