T CELL ABNORMALITIES IN AUTOIMMUNE MRL/1PR

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Murine SLE is an appropriate model for human SLE, since most, if not all of the immunological abnormalities fundamental to human SLE can also be readily observe in the murine system. The MHL1pr/1pr mouse is one of the strains that spontaneously develop SLE. In addition, all 1pr/1pr mice develop massive generalized lymph node enlargements as the disease progresses. In these enlarged lymph nodes, more than 90% of the cells are T cells. This project is concerned mainly with the in vitro physiology and immunobiology of the abnormal T cells in 1pr/1pr mice, and the relationship between in vitro T cell abnormalities and development of autoimmunity in vivo. Our research goals are summarized as follows: 1). Characterization of responsiveness of each individual T cell subpopulation in 1pr/1pr mice to receptor driven activation signals or polyclonal activators. 2). Characterization of the consequence of activation in vitro with respect to cell surface phenotypes and their differentiation state. Correlation between in vitro observations and in vivo pathogenesis. 3) Characterization of immune abnormalities in vitro and the establishment of an in vitro model system for the study of differentiation of 1pr/1pr T cells.