Discussion

Regulatory T cells (Tregs) are a small fraction of the CD4-positive T cell pool. Being able to suppress the function of effector T cells, Tregs play important roles in maintaining immunological self-tolerance and thereby avoiding auto-immune diseases. However, under certain medical conditions like cancer, this suppressive capability can facilitate the development and progression of the disease. In fact, accumulation of Tregs in tumour microenvironments is a common feature of many different cancers and has been linked to poor prognosis. As a consequence, various approaches already tried to hamper Treg function in cancer patients.
Among other markers like high expression of CD25 (IL-2 receptor alpha chain) and low expression of CD127 (IL-7 receptor subunit alpha), Tregs are best delineated by stable expression of the transcription factor forkhead box P3 (FoxP3). We therefor established a fully automated high throughput protocol enabling us to measure intra cellular FoxP3 antibody staining by flow cytometry using the 384-well plate format. Screening different small molecular compound libraries on primary human T cells using FoxP3 expression as readout, we hope to find novel modulators of FoxP3 expression and Treg function