Thymic epithelial injury in graft-versus-host reactions following adrenalectomy

In four separate experiments 140 adults A(H-2a) x C57BL/6(H-2b) F1hybrid mice were surgically adrenalectomized and divided into three experimental groups. Seventy-one additional adult F1hybrids (AXC57BL/6) which had not been adrenalectomized were divided into three similar groups. In Group 1 (GvH group), GvH reactions were induced by the injection of 50 x 106 pooled parental lymphoid cells intravenously. The second group (syngeneic group) received 50 x 106 pooled F1 hybrid lymphoid cells intravenously. The third group (uninoculated group) received no lymphoid inoculum. At regular intervals the animals were killed, autopsied, and histologically studied. Visceral alterations of GvH reaction were recorded in the thymus, lymph nodes, spleen, and liver in the GvH groups; none was present in the other groups. The thymuses in the nonadrenalectomized GvH group underwent prompt involution characterized by size reduction and cortical lymphoid cell depletion. These changes were not apparent in the GvH adrenalectomized group. Both GvH groups, however, demonstrated an effacement of the medulla, lymphocyte incursion into the medulla, lymphocyte emperipolesis of medullary epithelial cells, gradual disappearance of Hassall's corpuscles, epithelial cell injury, and an ingress of macrophages laden with nuclear and cellular debris. This study suggests that the stress and corticosteroid response which accompany a GvH reaction account for the reduction in the thymic size and cortical lymphoid cell mass. The medullary alterations, therefore, would appear to be initiated by the GvH reaction per se.