Treatment of NZB/NZW mice with total lymphoid irradiation: long-lasting suppression of disease without generalized immune suppression.
We used total lymphoid irradiation (TLI; total dose = 3400 rad) to treat the lupus-like renal disease of 6-mo-old female NZB/NZW mice. Similar to our past studies, this treatment resulted in a marked prolongation of survival, decrease in proteinuria, and decrease in serum anti-DNA antibodies compared with untreated littermate controls. Although there was no evidence of disease recurrence in TLI-treated mice until after 12 mo of age, the in vitro proliferative response to phytohemagglutinin by NZB/NZW spleen cells recovered within 6 wk such that responses were greater than control NZB/NZW animals. A similar recovery and overshoot after TLI were evident in the primary antibody response to the T cell-dependent antigen sheep red blood cells (SRBC). Both the total and IgG anti-SRBC antibody responses after TLI were greater than those of untreated NZB/NZW controls, and were comparable with those of untreated non-autoimmune mice. Despite this increased response to mitogens and antigens after TLI, we noted a decrease in spontaneous splenic IgG-secreting cells and a decrease in IgG but not IgM antinuclear antibody production. Nonspecific suppressor cells of the mixed leukocyte response were detectable in the spleens of NZB/NZW mice early after TLI. However, the disappearance of suppressor cells was not associated with recrudescence of disease activity. Furthermore, transfer of large numbers of spleen cells from TLI-treated NZB/NZW mice did not result in disease suppression in untreated age-matched recipients. In summary, treatment of NZB/NZW mice with TLI results in a prolonged remission in autoimmune disease, which is achieved in the absence of generalized immunosuppression.
D000818:Animals; D000921:Antibody-Producing Cells / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology* / Q000503:physiopathology; D001402:B-Lymphocytes; D005260:Female; D007126:Immunoglobulin Allotypes / Q000096:biosynthesis; D007165:Immunosuppression Therapy / Q000379:methods; D007958:Leukocyte Count / Q000528:radiation effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D010835:Phytohemagglutinins / Q000494:pharmacology; D013154:Spleen; D013601:T-Lymphocytes; D013997:Time Factors; D014916:Whole-Body Irradiation
D007126:Immunoglobulin Allotypes; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins