Dauphinee M J, Talal N, Goldstein A L, White A
Proc Natl Acad Sci U S A. 1974 Jul;71(7):2637-41. doi: 10.1073/pnas.71.7.2637.
New Zealand Black (NZB) mice develop after 16 weeks of age an autoimmune and lymphoproliferative disease which is a model for systemic lupus erythematosus and lymphoid malignancy in humans. At this age, the mice manifest a progressive decline in T lymphocyte (thymus-derived lymphocyte) functions and serum thymosin levels. Thymocytes from 8-week old NZB mice exhibit an abnormal DNA synthetic response when transplanted into lethally irradiated C57B1/6 recipients. DNA synthesis (measured as the incorporation of radioactively labeled 5-iodo-2'-deoxyuridine) is delayed in onset and still increasing 6 days after cell transfer. By contrast, 2-week old NZB thymocytes show a normal response which is rapid in onset and completed by day 6.NZB mice were injected with thymosin fraction 5 or with bovine serum albumin starting at 2 weeks of age. Thymocytes from 8-week old thymosin-treated mice showed a normal DNA synthetic response, whereas the albumin-treated controls showed the abnormal response expected at this age. The ability of thymosin to correct the DNA synthetic response was related to dose and duration of treatment. These results suggest that thymosin can induce a more normal state of thymocyte differentiation in NZB mice. If abnormal thymocyte differentiation is related to the subsequent emergence of autoimmunity and lymphoid malignancy, then continuous treatment with thymosin may have therapeutic potential. These experiments suggest that an endocrine disturbance may contribute to autoimmune and lymphoproliferative disease in NZB mice and possibly in humans.
新西兰黑鼠（NZB）在16周龄后会患上一种自身免疫性和淋巴细胞增殖性疾病，这是人类系统性红斑狼疮和淋巴恶性肿瘤的模型。在这个年龄段，小鼠的T淋巴细胞（胸腺来源的淋巴细胞）功能和血清胸腺素水平会逐渐下降。将8周龄NZB小鼠的胸腺细胞移植到经致死剂量照射的C57B1/6受体小鼠体内时，会表现出异常的DNA合成反应。DNA合成（通过放射性标记的5-碘-2'-脱氧尿苷掺入来测量）开始延迟，在细胞转移后6天仍在增加。相比之下，2周龄NZB小鼠的胸腺细胞表现出正常反应，反应开始迅速，在第6天完成。从2周龄开始，给NZB小鼠注射胸腺素5组分或牛血清白蛋白。8周龄经胸腺素处理的小鼠的胸腺细胞表现出正常的DNA合成反应，而经白蛋白处理的对照组则表现出这个年龄段预期的异常反应。胸腺素纠正DNA合成反应的能力与治疗剂量和持续时间有关。这些结果表明，胸腺素可以诱导NZB小鼠胸腺细胞分化进入更正常的状态。如果异常的胸腺细胞分化与随后自身免疫和淋巴恶性肿瘤的出现有关，那么持续用胸腺素治疗可能具有治疗潜力。这些实验表明，内分泌紊乱可能导致NZB小鼠以及可能人类的自身免疫和淋巴细胞增殖性疾病。
