My graduate thesis was in the field of Reproductive Immunology specifically, the study of immune responses and ovarian function in primates immunized with egg protein antigens. My post-doctoral work was on the development of Contraceptive Vaccine in primates in Dr. Tung's laboratory, a part of the Center for Recombinant Gamete Contraceptive Vaccinogens at the University of Virginia (UVA). I had to take a break in my research for over one year due to family health problems. I returned to Dr. Tung's lab in July 2000 to complete and publish my post-doctoral work. At this time, Dr. Tung's lab was studying the loss of CD4+CD25+ regulatory T cell function induced by neonatal thymectomy between days 1-4 after birth (d3tx) as a cause of organ specific autoimmune disease. In addition, Drs. Fu, Tung and McDuffie had established a Specialized Center of Research for Systemic Lupus Erythematosus (SLE) at UVA. I got interested in the mechanisms of immunoregulation and initiated a project to study the role of regulatory T cells in SLE, which is a systemic autoimmune disease affecting multiple organs and characterized by the presence of circulating autoantibodies (Aab) to nuclear and cytoplasmic antigens. The project has given us exciting leads for future study and form the basis of the present proposal. We will use the d3tx model of CD4+CD25+ regulatory T cell depletion in murine SLE. Two mouse strains studied, SNF1 and NZM2328, spontaneously develop Aab and fatal glomerulonephritis (GN). D3tx in SNF1 mice accelerated Aab but protected from fatal GN. In contrast, d3tx exacerbated Aab and GN in NZM2328 mice compared to sham thymectomized (stx) mice. In addition, reconstitution of d3tx NZM2328 mice with CD25+T cells prevented exacerbation of SLE. These data suggest the hypothesis that CD4+CD25+ regulatory T cells influence induction of SLE in NZM2328 mice. Spontaneous SLE in NZM2328 has a gender bias, predominantly affecting females. However, depletion of regulatory T cells by d3tx results in comparable GN in both sexes. This leads to the second hypothesis that regulatory T cell function dictates the gender bias of GN in NZM2328 mice. I had a productive post-doctoral fellowship in the area of Reproductive Immunology, however, additional training in cellular immunology and renal pathology would be essential for my development as an independent scientist in lupus research. This award will help to overcome the lag period in my career induced by my leave of absence and return to a new field of study, and will facilitate my aim of becoming an independent scientist.
