Influence of thymic genotype on the systemic lupus erythematosus-like disease and T cell proliferation of MRL/Mp-lpr/lpr mice.

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Abstract
In young adulthood, MRL/Mp-lpr/lpr mice develop a severe systemic lupus erythematosus(SLE)-like syndrome associated with massive T cell proliferation. The congenic MRL/Mp-+/+ mice lack the lrp gene and develop chronic SLE late in life. Thymic transplants were exchanged between these substrains to determine the role of the thymus in the development of early, severe SLE and lymphoproliferation. The median survival times of unmanipulated lpr/lrp and +/+ mice were 160 and 510 days, respectively. The lpr/lpr and +/+ mice thymectomized when newborn and transplanted at 1 mo. with the opposite type of thymus retained the diseases phenotype of their unmanipulated counterparts with 50% mortality at 186 and 498 days, respectively. lpr/lpr mice thymectomized when newborn but not transplanted with thymus did not develop lymphoid hyperplasia and glomerulonephritis and 100% were alive at 390 days. Serologically, the thymectomized but untransplanted lpr/lpr mice had significantly reduced levels of autoantibodies; thymectomized and transplanted mice of either substrain were similar to unmanipulated controls. A thymus evidently is essential for expression of lymphoproliferation and early SLE-like disease in the lpr/lpr phenotype. The lpr/lpr disease is not a result of a unique hormonal or microenvironmental defect(s) of the thymus of this substrain because the genotype of the thymus is irrelevant for the development of T cell proliferation and early SLE. Differentiation of +/+ stem cells under the hormonal or microenvironmental influences of a thymus that possess the lpr genotype apparently does not lead to abnormal T cell differentiation or early autoimmunity, and the lpr/lpr disease cannot be caused exclusively by an intrinsic B cell defect or environmental stimuli that cause B cell polyclonal activation.