"A revolution in the basic understanding of immunology occurred in the late 1980s with the discovery that CD4+ helper T cells were not a homogeneous population but could be divided into Th1 and Th2 subsets based on their cytokine profiles. 20 years later the field of T cell subset phenotype and function remains fast moving with the recently demonstrated existence of T regulatory and Th17 cells adding extra layers of complexity. The meeting will explore current ideas about the roles played by these varied T cells subsets in a variety of infections with presentations from leaders in the field" Meeting Chair: Dr Kathryn Else, University of Manchester, UK
9:00 – 9:45 Registration
9:45 – 10:00 Morning Session - Introduction by the Chair: Dr Kathryn Else, University of Manchester, UK
10:00 – 10:30 Conditional mouse mutants as a tool to analyse Th1, Th2, Th17 and Treg subsets in parasite infection
Professor Werner Mueller, Manchester, UK
10:30 – 11:00 CD4+ T helper subsets in Helicobacter hepaticus infection: Th1, Th17, and Treg cells.
Dr Marika Kullberg, University of York, UK
Inflammatory bowel disease, including Crohn’s disease and ulcerative colitis, is a chronic inflammatory disorder of the gastrointestinal tract that is caused in part by an inappropriate immune response to intestinal microbiota. To help our understanding of the process by which bacteria induce inflammation in the gut, our lab is using an experimental model of colitis involving infection with Helicobacter hepaticus. This model allows us to examine the early events following bacterial challenge, and to analyze bacterium-specific CD4 T cell responses in disease-susceptible versus disease-resistant hosts. The H. hepaticus colitis model also provides a platform by which to elucidate the role of bacterium-specific CD4 T cells and their cytokines in the inflammatory process in the intestine.
11:00- 11:05 Speakers photo
11:05 – 11:30 Mid-morning break
11:30 – 12:00 Regulatory T cell populations in human and murine malaria
Professor Eleanor Riley, London School of Hygiene and Tropical Medicine, UK
Acute, highly virulent infections are accompanied by florid - typically type 1- immune responses which need to be tightly regulated to avoid induction of immune-mediated pathology. In both murine and human malaria infections, immune regulation is mediated by IL-10 and TGF-beta. These cytokines emanate from a variety of cell types including several populations of T lymphocytes. I will present data from murine and human studies on the roles of IL-10, TGF-beta, monocytes, classical (natural or endogenous) regulatory T cells and induced (effector) T cell populations in the regulation of parasite control and immunopathology.
12:00 – 12:30 T helper phenotypes in infectious disease
Professor Janette Bradley, Nottingham, UK
12:30 – 12:40 Introduction to the Biopark
12:40 – 13:30 Lunch and Poster Viewing
13:30 – 14:00 Immune responsiveness to schistosome infection
Dr Adrian P. Mountford,The University of York, UK
14:00 – 14:15 Selected Oral Presentation1
14:15 -14:45 Invited Speaker to be confirmed
14:45 – 15:15 Afternoon Tea/Coffee and Last Poster Viewing
15:15- 15:45 The development and interactions of regulatory and effector T cell responses during helminth infections
Dr Matthew Taylor, University of Edinburgh, UK
Human helminth infections are synonymous with suppression of the host immunity resulting in parasite survival and the maintenance of chronic infections. Using a murine model of filariasis, Litomosoides sigmodontis infection of susceptible (BALB/c) and resistant (C57BL/6) mice, we have shown that T cell regulation occurs at two levels; through a CD4+Foxp3+ regulatory T (Treg) cell response and the development of CD4+ effector T (Teff) cell hypo-responsiveness. The CD4+Foxp3+ Treg cell response is initiated by the infective L3 stage rapidly upon contact with the host, with increased CD4+Foxp3+CD25+ Treg cell proliferation in vivo resulting in a dominant expansion of CD4+Foxp3+CD25+ T cells. Depletion of CD25+ Treg cells prior to infection enhances parasite clearance indicating that the Treg cell response inhibits protective immunity and is mainly recruited from the pre-existing pool of natural CD4+Foxp3+ Treg cells. The second level of T cell regulation develops as infection establishes and the CD4+ Teff become intrinsically hypo-responsive to antigenic stimulation. This is associated with enhanced expression of CTLA-4, GITR, and PD-1. Once established, infection-induced suppression can be overcome by depleting CD25+ Tregs, but only if combined with restoring Teff cell responses by providing co-stimulation through GITR, or blocking co-inhibition through CTLA-4. As yet, it is not known what factors drive the initial bias towards a Treg response or the later Teff cell hypo-responsiveness. Our hypothesis is that the balance of co-stimulatory/ inhibitory signals during T cell priming and maintenance determines whether regulatory or effector responses prevail, with a lack of co-stimulation or a bias towards co-inhibition resulting in immune suppression. Initial work shows an important role for GITR in Th2 cell priming as blocking GITRL in resistant C57BL/6 mice ablates the Ag-specific Th2 response (IL-4, IL-13) and results in a Th1 phenotype (increased IFN-y). Additionally, co-stimulating susceptible BALB/c mice with an agonistic anti-GITR mAb enhances their Ag-specific Th2 response. We are currently investigating whether a bias towards co-inhibition favors a regulatory environment using blocking antibodies against PD-1 and its ligands. To further delineate Th2 responses following infection and treatments, as well as interactions between Treg and Teff cells, we are using BALB/c 4get IL-4gfp mice to track and quantify Th2 cells. Overall we believe that the initial T cell priming to filarial helminths is critical in determining whether the host will succumb to or resist parasite immunomodulation. Co-stimulatory/inhibitory signals play a role in the development of T cell responses against L. sigmodontis and therapeutic manipulation of these pathways could be used to enhance immune priming and restore protective immunity.
15:45 – 16:00 Selected Oral Presentation2
16:00 – 16:30 Invited Speaker to be confirmed
16:30 - 17:00 Regulation of infection by gastrointestinal nematodes
Professor Richard Grencis, University of Manchester, UK
17:00 – 17:30 Chairman’s summing up.
