New Zealand mice develop a naturally occurring thymocytotoxic antibody (NTA) which increases in titer with age. This antibody causes a loss of recirculating peripheral T cells and interferes with T cell functions. To study the potential pathogenic role of NTA in murine autoimmune disease, NZB/W mice were injected daily with NTA-containing serum starting at 3 to 5 days of age. Littermate controls received normal mouse serum (NMS). After 4.5 weeks of treatment, spleen cells from female NZB/W mice treated with NTA had a significant increase in capacity to induce graft-vs-host disease in newborn Swiss mice, suggesting a deficiency of suppressor cells.
Con A-activated spleen cells from NMS-treated animals suppressed IgM synthesis in vitro; however, Con A-activated spleen cells from NTA-treated mice were not suppressive. The NTA-induced loss of suppressor cell function was prevented by prior absorption of the NTA with thymocytes. Cells from control (NMS-treated) and NTA-treated litter-mates responded similarly to mitogens (Con A, PHA, PWM, LPS) and allogeneic lymphocytes in vitro. Although the number of nucleated spleen cells and splenic B cells was not changed by NTA treatment, a moderate reduction of T cells was seen (37% to 26% Thy 1.2 positive cells). Nevertheless, NTA treatment did not alter either skin allograft injection or the antibody response to immunization with the T-dependent antigen SRBC.
These studies suggest that NTA causes a selective loss of suppressor cells in NZB/W mice, supporting the hypothesis that NTA may play a pathogenic role in murine autoimmunity.