Dr. Tse's laboratory is studying the genetic regulation of immune functions. He uses murine experimental autoimmune encephalomyelitis (EAE) as an animal model to explore the genetic factors that allow the recognition of autoantigens. EAE is a demyelinating disease of the central nervous system (CNS) and is mediated by T cells specific for myelin antigens. Certain mouse strains are highly susceptible to experimentally induced disease while others are less susceptible. A long-term goal of the laboratory, therefore, is to understand how these latter strains resist disease induction. Experiments are designed to determine the role of the T cell receptor (TCR) genes and genes of the major histocompatibility complex (MHC) in the disease induction process. Recent data using gene mutants and knock-out mice also suggest that normal expression of Fas and CD1 in host cells are required for induction of adoptive EAE.

To track the migration of T cells into the CNS, Dr. Tse has constructed a new mouse strain that differs from the highly susceptible SJL mouse only in the Thy-1 cell surface antigen. By transferring encephalitogenic donor cells into naive Thy-1 congenic recipients, it is now possible to identify donor cells in the CNS of the recipients during the various stages of disease development with specific anti-Thy-1 antibodies. Using this technique, Dr. Tse is trying to determine the characteristics of CNS-seeking T cells and their trafficking patterns during acute disease, remission and relapses.

Once recovered from acute EAE, some mouse strains spontaneously relapse. The development of relapsing EAE appears to be associated with genes of the MHC. Interestingly, the F1's between a relapsing strain (e.g., H-2s) and a non-relapsing strain (e.g., H-2b) exhibit the non-relapsing phenotype. One of the current projects in the laboratory, therefore, is to use genetic and molecular techniques to determine the nature of the tentative genes that regulate this phase of disease.