The effect of the genetic background on the development and function of accumulating YE1/19.1+ cells in lpr mice

It has been demonstrated that the single autosomal recessive lpr gene is capable of inducing autoimmunity in various strains of mice. Moreover, it is generally accepted that this is an indirect effect of the accumulation of an unusual T lymphocyte subset. Although a thymus is essential for the initiation of the lymphadenopathy, adult thymectomy cannot delay the development of the disease. In this study we report that the degree of lymphadenopathy can be assessed utilizing the YE1/19.1 monoclonal antibody. This antibody recognizes a surface antigen found on the EL 4 tumor lines and all "double negative" nonresponsive T cells from lpr gene expressing mice. We then constructed radiation-induced chimeras to determine whether a normal thymic and extrathymic milieu had any effect on the development and function of the YE1/19.1+ T cells responsible for the lymphadenopathy. It was found that the spleens of B6-lpr----B6-lpr chimeras demonstrated a marked accumulation of the YE1/19.1 positive cells. However, the spleens of B6-lpr----B6 chimeras were shown to contain very few YE1/19.1 positive cells. These differences were also reflected in the amount of anti-DNA antibodies produced by each of the chimeras, the B6 recipients producing very little autoantibody. Once isolated by panning it was found that the cells from either chimera failed to respond to mitogenic signals. Our findings support the possibility that the lpr gene can function in the thymus and/or the periphery of the animal to limit the numbers of accumulating T cells.