Immunotherapy of graft versus host disease with specific alloantiserum: restoration of cerebellar development in infant rats

Abstract

Fischer (FI) rats were stimulated to produce high-titre alloantiserum against DA antigens for alleviation of the symptoms of graft versus host disease (g. v. h. d.) in FI neonates. G. v. h. d. was procured by intravenous injection of DA lymph node cells on the day of birth. Daily injections of alloantiserum on postnatal days 11–13 not only prevented the progress of the disease in the whole animal but reversed the altered neuronal histogenesis that was present in diseased animals at day 11. Specifically, by 3 days after onset of alloantiserum treatment, the severely depressed DNA synthesis had returned to near normal levels. The decreased numbers of newly formed cells in the cerebellar cortex matrix area seen at day 11 was also reversed. For example, there was a significant increase in the number of newly formed basket and stellate cells in 14 day old alloantiserum-treated animals. G. v. h. d. did not result in a lymphocytic infiltration or an inflammatory response in the cerebellum. Therefore, we postulate that the deleterious effects of g. v. h. d. and the restoration effects of alloantiserum treatment are not directly cell-mediated. Rather, some soluble factor(s) interfering with the cerebellar cell cycle may be released during the interaction of donor lymphocytes and host cells at sites distant from the cerebellum. In support of this, in vitro analysis of DNA synthesis revealed that removal of cerebellar cells from the internal milieu of g. v. h. d. permitted DNA synthesis to proceed at a rate similar to that in control tissue.