Treatment of NZB/NZW mice with total lymphoid irradiation: long-lasting suppression of disease without generalized immune suppression.
Treatment of NZB/NZW mice with total lymphoid irradiation: long-lasting suppression of disease without generalized immune suppression.
复制标题
用全淋巴照射治疗 NZB/NZW 小鼠：持久抑制疾病，而不抑制全身免疫。
作者：
B. Kotzin;R. Arndt;S. Okada;R. Ward;A. Thach;S. Strober
采用总剂量3400rad的全淋巴照射治疗6月龄雌性NZB/NZW小鼠狼疮性肾病。与我们过去的研究类似，与未治疗的窝仔对照组相比，这种治疗显著延长了存活期，减少了蛋白尿，并降低了血清抗DNA抗体。尽管TLI治疗的小鼠直到12个月龄后才有疾病复发的证据，但NZB/NZW脾细胞对植物血凝素的体外增殖反应在6周内恢复，因此反应强于对照NZB/NZW动物。在TLI后，对T细胞依赖抗原绵羊红细胞(SRBC)的一次抗体反应也明显出现类似的恢复和超调。TLI组小鼠血清中抗SRBC的总抗体和免疫球蛋白抗体水平均高于NZB/NZW对照组，与未治疗的非自身免疫小鼠相当。尽管TLI后对有丝分裂原和抗原的反应增加，但我们注意到自发的脾免疫球蛋白分泌细胞的减少和免疫球蛋白G的减少，但没有产生免疫球蛋白M抗核抗体。TLI后早期，NZB/NZW小鼠的脾中可检测到混合白细胞反应的非特异性抑制细胞。然而，抑制细胞的消失与疾病活动的复发无关。此外，移植大量来自TLI治疗的NZB/NZW小鼠的脾细胞并没有导致未经治疗的年龄匹配的受者的疾病抑制。总之，用TLI治疗NZB/NZW小鼠可以延长自身免疫性疾病的缓解时间，这是在没有全身性免疫抑制的情况下实现的。
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.