Suppression of lymphoproliferation and auto-immunity by elimination of a radiosensitive bone marrow cell in mice bearing the lpr gene.

The autosomal recessive lpr gene (lymphoproliferative) has been bred into several normal strains of mice. Although the time of disease onset may vary, all of these lpr mice develop hypergammaglobulinaemia, antibodies to nucleoproteins, and massive lymphoproliferation. The abnormalities do not appear in their normal congenic counterparts, which lack the lpr gene. We studied the effects of sublethal whole-body X-irradiation (300 rads) on disease features and lymphocyte subpopulations by using flow cytometry. H-2k strains, C3H and MRL/++ and their autoimmune lpr counterparts, were killed at 1, 2, 4, 8 and 24 weeks after irradiation, which was given at 6-8 weeks of age. In the lpr mice, lymphoproliferation, autoimmunity, mortality and number of Ia+ cells were greatly reduced in the irradiated mice compared with nonirradiated controls. Abnormal cytofluorometric patterns seen with lpr thymocytes were corrected by the low-dose irradiation treatment. In addition, lethally irradiated lpr mice reconstituted with syngeneic bone marrow from low-dose irradiated mice exhibited retarded development of autoimmune disease. We conclude that the lymphoid alterations induced by X-irradiation reflect a recovery of immunologic control associated with suppression of autoimmune manifestations.