The response of the reticuloendothelial system to skin transplantation. The cellular basis of hepatosplenomegaly in mice bearing skin grafts and its significance.

Abstract

SummaryBalb/c mice bearing small, medium and massive skin allografts developed hepatosplenomegaly. The increased liver mass, found also in mice with massive isografts, was due to hypertrophied hepatocytes. These enlarged cells were seen in electron micrographs to contain increased amounts of rough‐ surfaced endoplasmic reticulum, and biochemical estimations revealed increased concentrations of ribonucleic acid. It is likely that the increase in liver mass and ribonucleic acid formation represents a hypertrophic response which provides increased amounts of (a) purines, and thereby sustains the intense cellular proliferation in lymphoid tissues, and (b) plasma proteins, notably α‐ and β‐globulins and fibrinogen which are known to be elevated following surgery or trauma.Mice bearing 4 cm2 and 8 cm2 isografts and allografts showed splenomegaly which reached a maximum between 8 and 12 days after transplantation; in the case of 4 cm2 allografts. a second peak of splenic enlargement occurred at 22 days. The spleens of isografted mice showed increased erythropoiesis but little change in the lymphatic nodules. Allografted mice showed intense granulo‐ poiesis as well as increased erythropoiesis during the first peak of splenomegaly; the second peak was characterized by normal haematopoietic activity and a marked enlargement of lymphatic nodules with prominent germinal centre development. Mice with massive allografts showed some evidence of germinal centre formation in their spleens at about the time of allograft rejection, but did not exhibit a second peak of splenomegaly nor a cellular response indicative of intense antibody formation such as that seen in mice with 4 cm2 allografts. If the prolonged survival of massive allografts is due to a depression of immuno‐ logical capacity resulting from the sequelae of severe surgical trauma, as previously suggested, then the inability of mice with massive allografts to monnt a total humoral antibody response may reflect another aspect of their immuno‐ logical impairment.