Alteration in DNA synthetic response of thymocytes from NZB mice of different ages.

Thymocytes from NZB and DBA/2 mice were injected into lethally irradiated C57 B1/6 recipients. DNA synthesis in spleen and lymph node was measured as the incorporation of radioactive 5-iodo-2-deoxyuridine. The generation of cytotoxic effector cells was also studied in an in vitro cytotoxicity assay, with EL-4 lymphoma target cells. The kinetics of DNA synthesis were similar for 2- and 8-week-old DBA/2 donors and for 2-week-old NZB donors with a peak on day 4. Thymocytes from 8-week-old and 9-month-old NZB donors showed a delayed onset of DNA synthesis which was still increasing on day 6. When NZB donor thymocytes from 2- and 8-week-old mice were mixed together before injections, as few as 25% of 8-week-old cells gave a DNA synthetic response characteristic of this aged population. These results suggest an abnormal thymocyte development in NZB mice which may relate to the subsequent emergence of autoimmune disease.