Collective T cell behaviour in health and disease

Dr Audrey Gerard; Kennedy Institute, University of Oxford

Despite a remarkable degree of plasticity, stochasticity and functional heterogeneity in their individual response, T cell overall response to infection is consistent and robust. This implies a coordinated response across a system-wide level to facilitate the control of pathogens while maintaining self-tolerance. Much research has focused on individual T cell activation and differentiation, but how the stochastic individual responses are integrated is unknown. This global coordination can only be achieved by constant cellular communication between responding cells and has to be supported by the ecosystem they reside in. In this presentation, I will focus on the impact of CD8 T cell communication through the cytokine IFNg. I will present data supporting the existence of IFNg driven T cell communication during infection, and its relevance for T cell response. I will then move on to situation where IFNg production is chronic, namely during immune response to tumours, and present data demonstrating that chronic IFNg signalling in T cells restricts their anti-tumour response by inhibiting stem-like T cell maintenance.

I am an Associate Professor and Senior Research Fellow of the Kennedy Trust of Rheumatology Research (KTRR) at the University of Oxford.

My previous research focused on the characterization of relevant cellular and molecular events regulating the initiation of immune responses. I completed my Ph.D. under the supervision of Jacques Nunes and Daniel Olive at the University of the Mediterranean, Marseille, France, focusing on the negative regulation of primary and leukemic T cell activation. I undertook postdoctoral training at the Netherlands Cancer Institute in Amsterdam with John Collard, where I studied polarity proteins and T cell migration. I then moved on to the laboratory of Matthew Krummel at UCSF, San Francisco, USA, where I continued to work on the molecular mechanism of T cell migration in vivo using 2-photon microscopy. In addition, I developed a broader interest in the spatio-temporal behaviour of T cells during infection and vaccination. In particular, I described a specific period during which T cells directly communicate to control each other's fate. I joined the Kennedy Institute in June 2016, where I am still exploring the dynamic of T cell immune responses.