Cellular Immunology Laboratory
P.I. Mucosal Immunology Laboratory
Senior Lecturer Biology Department, NUIM
The human immune system has to respond effectively to a multitude of microbes, but must be tolerant of self tissue, and not respond aggressively against the developing foetus. We are asking the deep-seated questions: “How is immunity switched on?”, “How is it turned off?”, “How does the body reject or tolerate mis-matched tissue?” and “Can we manipulate these responses to improve human health?” Asking these questions has led us to explore two inter-related themes: 1) the immunology of a type of adult stem cell- the mesenchymal stem cell and 2) the cell mediated immune response to new vaccines (suitable for neonates).
These two themes may seem disconnected but at a fundamental level they are both linked by the process through which the adaptive immune system is initiated and shaped. Therefore, we examine the dendritic cell (a sentinel cell which is important for initiating adaptive responses) and the CD4+ T cell (the cell which essentially co-ordinates and controls both tolerance and effector responses).
Theme 1: Adult Stem Cells: Cells which Shape Immunity. The clinical use of adult mesenchymal stem cells holds great promise for regenerative medicine. With our academic and clinical partners in REMEDI and elsewhere, we are taking stem cell therapies to human trial for a variety of conditions. However, such approaches face the challenge of immune rejection of mismatched tissue (allogeneic rejection). Our group have shown three remarkable features of these stem cells which may mean that adult derived stem cells might be used in a wide variety of new therapies. First we have shown how CD4+ T cells alter or “license” these stem cells, making them less amenable to rejection; second the stem cells themselves alter dendritic cells to dampen immunity, and finally the stem cells induce a type of regulatory CD4+ T cell that suppresses rejection. Thus there is an elaborate cross talk between the immne system and the stem cell to bring about tissue repair. In effect, stem cells create a tolerogenic milieu. We are uncovering the fundamental processes that will benefit future patients, and support new biotechnology and pharmaceutical industries.
Theme 2. Understanding Cellular Immunology: better vaccines for neonates. Our vaccine studies have focused on pathogen-host interactions during B. pertussis infection (the causative agent of the childhood disease, whooping cough). With our academic partners, we have shown that efficacious vaccines generate a type of immunity dominated by IFN-g production whereas less efficacious vaccines generate a different type of response. Here too our focus is on the use of sophisticated models to determine the role of CD4+ T cells and dendritic cells. This work has led to advances in vaccine adjuvant design resulting in high quality publications and patents with industrial partners and new ways to make safer vaccines. We are currently working with the Institut Pasteur de Lille and our EU (Framework 7) partners in project “Child-Innovac”, that will bring a new whooping cough vaccine for neonates to human clinical trial.
Finally the Lab. has a strong commitment to the Combating diseases of Poverty Consortium and confronting the poverty related diseases of TB, HIV and malaria. Each year we send Masters students to East African partner Universities and host African students in the lab as part of Irish Aid funded training exchange. We also perform outreach activities with local teachers and schools to promote the value of scientific career paths.
Prof. Camille Locht, Institut Pasteur de Lille, France,
Prof. Frank Barry, REMEDI, NUI Galway, Ireland.
Professor Jim Johnston, Queen’s University Belfast.
Prof. Joe Cassidy, UCD, Dublin, Ireland.
Dr Catherine Flynn, Haematology, St.James’ Hospital Dublin.
Dr Stephen Lane, Respiratory medicine, AMNCH, Tallght.
Dr Tim O’Brien, NUI Galway, Ireland.
Enterprise Ireland , Health Research Board, EU FP6 Marie Curie Transfer of Knowledge, SFI, HEA PRTLI.