A joint RCAI/JSI meeting "Development and Maintenance of the Immune System" was held July 26th and 27th at the Pacifco Yokohama Conference Center. Speakers were invited from Japan, Canada, Germany, the UK, and the US. Among the participants in this meeting were the students from the RCAI International Summer Program and some of the lecturers from that program also spoke here.
The first day's talks concerned the development of the immune system and mechanisms of lymphocyte selection. Dr. Toshio Suda (Keio University) focused on a very early developmental stage, the hematopoietic stem cell (HSC). He described the importance of the osteoblast, a cell normally thought of in terms of its role in bone formation, in the stem cell niche, a specialized microenvironment where the HSC reside in a quiescent state. Dr. Juan Carlos Zúñiga-Pflücker (University of Toronto, Canada) demonstrated an important role for Notch signaling in early T cell development. A Notch signal is required for expansion of αβ T cells and their survival at the single positive stage and PI3 Kinase and Akt are downstream effectors. By contrast, the γδ T cells can survive without Notch once they express a TCR. Dr. Al Singer (NIH, USA) described an interesting mouse model in which the TCR co-receptors CD4 and CD8 are deleted and signaling to the developing thymocytes occurs strictly through the TCR. Remarkably, if the major histocompatibility complex (MHC), which is normally what thymic T cells are selected on, is also inactivated, T cell development still takes place but the T cells in the periphery are not MHC restricted. Dr. Dianne Mathis (Harvard Medical School, USA) has been examining obesity and the role of low grade inflammation in adipose tissue in the development of type-2 diabetes. She found that regulatory T cells (Tregs) accumulate to an extraordinarily high fraction of CD4 T cells in the abdominal adipose tissue of mice as they age and that the cells have an unusual phenotype in comparison with Tregs in other tissues. Understanding the physiological role of these cells may provide new prophylactic treatment options for preventing diabetes.
Differentiation of lymphocyte subsets and the maintenance of a functional immune system were the focus of the second day's talks. Dr. Shinsuke Taki (Shinshu University) discussed basophils as a potential initial source of IL-4 for polarization of helper T cells toward the Th2 pathway. Analysis of gene targeted mice allowed him to define important regulatory molecules in IL-3 induced IL-4 production by basophils. Dr. Brigitta Stockinger (National Institute for Medical Research, UK) described physiological inducers for the development of Th17 cells, a recently described subset of helper T cells that produce IL-17. Zymosan, a yeast cell wall component and Mycobacterium tuberculosis were found to induce Th17 cells. She also noted that reported differences between human and mouse Th17 cells may not be real, but rather are an artifact of not starting with sufficiently pure naïve T cells when inducing human Th17 cell development in vitro. Dr. Marc Jenkins (University of Minnesota Medical School, USA) discussed strategies to enumerate polyclonal antigen-specific CD4 T cells in unimmunized mice in order to avoid the use of transferred TCR transgenic T cells to study the expansion and half life of these cells during an immune response. The frequency of peptide specific T cells is remarkably low and varies among different peptide epitopes, e.g. 220 versus 20 cells per mouse. The memory T cells generated after immunization decline slowly over time, with a half life of ~ 50 days for the one specificity studied in detail, and this may account for the loss of T cell immunity. Dr. Masato Tanaka (RCAI) has developed a system for tolerance induction in experimental autoimmune encephalomyelitis (EAE), a mouse model for human multiple sclerosis. Apoptotic cells expressing EAE self antigens are injected intravenously and protect the mouse against subsequent induction of EAE. Conditional knockout mice were used to identify the marginal zone macrophages in the spleen as important mediators of tolerance induction.
The next RCAI-JSI International Symposium on Immunology is tentatively scheduled for June of 2008.