Thymosin Corrects the Abnormal DNA Synthetic Response of NZB Mouse Thymocytes

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Abstract
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.