Presented by Dr Di Yu
Head of Laboratory for Molecular Immunomodulation
Department of Biochemistry and Molecular Biology
and Department of Medicine, Monash University
Dr. Yu and his team are investigating the molecular mechanisms of T cells that regulate the competence and the balance of immune responses, with the aim to design new strategies to modulate the immune system to treat autoimmune disease, infection and cancer. His research is published in journals including Nature, Nature Immunology, Nature Medicine and Immunity. He is a recipient of the New Investigator Award from the Australasian Society for Immunology, and the International Research Award from the Australian Society for Medical Research, and the Excellence Award from the Australian National Health and Medical Research Council.
During unresolved infections, some viruses escape immunological control and establish a persistent reservoir in certain cell types, such as human immunodeficiency virus (HIV), which persists in follicular helper T cells (TFH cells), and Epstein-Barr virus (EBV), which persists in B cells. Here we identified a specialized group of cytotoxic T cells (TC cells) that expressed the chemokine receptor CXCR5, selectively entered B cell follicles and eradicated infected TFH cells and B cells. The differentiation of these cells, which we have called ‘follicular cytotoxic T cells (TFC cells), required the transcription factors Bcl6, E2A and TCF-1 but was inhibited by the transcriptional regulators Blimp1, Id2 and Id3. Blimp1 and E2A directly regulated Cxcr5 expression and, together with Bcl6 and TCF-1, formed a transcriptional circuit that guided TFC cell development. The identification of TFC cells has far-reaching implications for the development of strategies to control infections that target B cells and TFH cells and to treat B cell–derived malignancies.