Associate Professor Di Yu, The Yu Group - T-cell Immune Mechanism, Monitoring and Modulation (TIM3), JCSMR, ANU
The sophisticated immune defence mechanisms are essentially orchestrated by T cells. Not only can T cells directly kill infected and cancerous cells, but they also, through multiple subsets, fundamentally control the activation and function of other immune cell types. Therefore, targeted regulation of T cells subsets can efficiently modulate immune responses to treat many human diseases.
Very recently, my group discovered a novel subset of CD8+ T cells, termed ‘follicular cytotoxic T cells’ (Tfc cells). For the first time, we demonstrated that Tfc cells express B-cell follicle-homing chemokine receptor, CXCR5, which enables them to migrate to B cell follicles and eradicate infected follicular helper T (Tfh) cells and B cells. Tfc cells’ specific function to control the infection of Tfh cells was soon verified by several following studies on simian immunodeficiency virus (SIV)-infected macaques and human immunodeficiency virus (HIV)-infected humans. Therefore, promoting Tfc cell function to eliminate the key latent HIV reservoir in Tfh cells paves the way toward a potential functional HIV cure. Importantly, we found interleukine-2 (IL-2) specifically inhibited the differentiation of Tfc cells, which might explain the failure of IL-2 Immunotherapy to benefit HIV-infected individuals already taking antiretroviral therapies. On the other hand, IL-2 immunotherapy was shown to benefit patients with lupus in a clinical study conducted by rheumatologists and my group. Such low-dose IL-2 immunotherapy in autoimmune disease promoted the function of regulatory T (Treg) cells but suppressed pro-inflammatory Tfh and IL-17-producing helper T (Th17) cells.
These examples demonstrate the knowledge for the molecular mechanisms by which T cells control the competence and balance of the immune system could be utilised to design new strategies to modulate the immune system to treat autoimmune disease, infection and cancer.