Thymic involution in murine graft-versus-host reaction. Epithelial injury mimicking human thymic dysplasia

Abstract

Mild, moderate, and severe graft-versus-host (GVH) reactions were induced in four series of experiments in 71 CBA X A and C57BL/6 X A F1 hybrid mice. At regular intervals post-GVH reaction induction (Days 4-42), the animals were sacrificed, autopsied, and histologically studied. Visceral alterations of GVH reaction were recorded in the spleen, lymph nodes, liver, kidney, gut, and thymus. A spectrum of thymic changes was documented, ranging from obliteration of a definable cortex and medulla with loss of Hassall's corpuscles to marked involution with complete disappearance of the gland. Ultrastructural studies revealed damage to both lymphocytes and epithelial cells along with lymphocyte emperipolesis of epithelial cells, lymphocytolysis within epithelial cells, and accumulation of numerous autophagic vacuoles containing fragments of cellular debris within epithelial cells and histiocytes. The resemblance of these alterations to human thymic dysplasia as observed in primary immunodeficient conditions was striking. The theoretical implications of these studies for the pathogenesis of human congenital immunodeficiency states are considered.