Experimental studies of immunologically mediated enteropathy: IV. Correlation between immune effector mechanisms and type of enteropathy during a GvHR in neonatal mice of different ages

Abstract

We have used the intestinal phase of the graft-versus-host-reaction (GvHR) in unirradiated F1 mice as a model for enteropathy due to cell-mediated immunity (CMI). Injection of neonatal (CBA x BALB/c)F1 mice less than 48 h old with CBA spleen cells produced an acute GvHR, which was associated with runting and severe intestinal damage, characterized by villus atrophy. These animals developed specific cytotoxic T lymphocyte (CTL) activity and invariably died. In contrast, 7-day-old F1 mice with GvHR developed a proliferative GvHR, characterized by intense splenomegaly, NK cell activation and intestinal crypt hyperplasia. These mice did not lose weight, had no villus atrophy or CTL activity and all recovered. A similar proliferative phase was also found to precede the established GvHR in 1-2-day-old hosts. Induction of a GvHR in 5-day-old hosts produced a disease with some characteristics of both proliferative and destructive GvHR, with some mice developing weight loss and villus atrophy, while others showed only crypt hyperplasia and NK cell activation. However, there was very little specific CTL activity in any of these animals. These results indicate that markedly different forms of GvHR can be induced in mice during the first week of life and that these are associated with different pathological effects. Although the immunological mechanisms which are activated may also differ between the types of GvHR, our findings support the hypothesis that intestinal damage which includes villus atrophy is merely a progressive form of the delayed type hypersensitivity responsible for a proliferative enteropathy.