T CELL GENE EXPRESSION AND TRAFFICING IN EAE

这位候选人加入了免疫学系和

This candidate joined the faculty of Department of Immunology and Microbiology at Wayne State University in 1986 after six years at Merck & Co. Wayne State University is particularly strong in Neuroimmunology research. The candidate quickly seized the opportunity and had since developed a research program aiming at analyzing the T cell receptor gene expression as well as in vivo trafficking of encephalitogenic cells in the murine experimental autoimmune encephalomyelitis (EAE) model. A part of the trafficking study is currently funded by NIH. The study on T cell receptor heterogeneity is currently partly funded by a grant from the National Multiple Sclerosis Society. In addition, an overlapping application is under review at NIH. The immediate objective of the research program is to use a T cell surface antigen as a genetic marker to follow the in vivo trafficking of encephalitogenic cells leading to the development of EAE. Specifically, myelin basic protein (MBP)-specific donor Thy-1.2+ donor T cells will be injected into naive Thy-1.1+ recipients. The fate of the donor cells in the CNS and lymphoid tissues of the recipients will be followed by virtue of the Thy-1 marker which can be detected with monoclonal anti-Thy-1.2 antibodies. This approach is especially important for the investigation of the effector cell mechanisms in the spontaneously relapsing phase of the disease. The stable genetic marker, unlike radioisotope-labeled cells, can be traced over a long period of time. Recently, the candidate's laboratory made the discovery that additional antigenic challenge of cell transfer recipients can lead to disease development in many reputed 'resistant' strains of mice such as C57BI/6 and BALB/C. This experimental system opens up new avenues for studying the genetic basis of susceptibility to EAE induction. One approach is to examine the T cell receptor (TCR) gene usage by encephalitogenic cells from these two strains. The concept of limited heterogeneity in TCR gene usage has raised hope that perhaps modulation of autoimmune diseases can be achieved through manipulation of the TCR itself. It will be very important to confirm these findings in additional mouse strains other than PL and B10.PL, especially in mice that are normally resistant to disease induction. Eventually, this knowledge of disease resistance will be utilized to design therapeutic approaches to human demyelinating diseases. This research program is both challenging and rewarding. The award of a RCDA will enable the candidate to more aggressively pursue the objectives of the program and to foster closer interactions with neuroimmunology experts within and outside of the Department. As noted in the application, the candidate has the full support of the Department and the School.