An investigation into the immune functional, morphological, and histopathological alterations during the course of graft-versus-host reactions /

The relationship between various immune functions, tissue damage, and splenomegaly was investigated during the course of Graft-versus-host (GVH) reactions.The GVH-associated tissue lesions appeared at the time when both the T- and B-cell functions were severely suppressed and NK cell activity was at its peak and/or highly augmented. The development of tissue lesions correlated with donor NK cell activity. On the other hand, splenomegaly developed independently of both the NK cell activity as well as tissue lesions.Prolonged immunosuppression was associated with thymic dysplasia, but not splenomegaly. The immune functions recovered gradually, following severe suppression, and coincided with the gradual recovery of the thymus. The immune functional recovery was observed in the following order: LPS responsive B-cell functions; ConA responsive T-cell functions; PHA responsive T-cell functions; and finally T-cell dependent B-cell responses. T-cell functions of immunodeficient GVH mice could be restored only when the thymic medullary regeneration had occurred. In contrast, the restoration of NK cell activity of NK-depressed mice was independent of thymic dysplasia.These studies provide information regarding the possible mechanisms involved in inducing immunosuppression, tissue damage, and splenomegaly following GVH induction