The Croonian Lecture: The homograft reaction

Abstract

In this Croonian Lecture I shall try to give an outline of our present knowledge—and, by implication, our present ignorance—of the homograft reaction. I shall confine it almost exclusively to homografts of normal (as opposed to malignant) tissues, and, among normal tissues, almost exclusively to skin. Much will therefore be left out that was very well worth saying, and without the consolation of being quite sure that some things which will be said might not better have been left out. It will not be necessary to weigh down the text with too many citations of evidence, because the homograft reaction has been the subject of several reviews within the past 2 years.* It is a sign of rapid progress, and should therefore be a source of satisfaction to everyone except perhaps their authors, that these reviews are already to some extent out of date. What is the homograft reaction, and why should so many people be studying it so intently? To begin with matters of terminology, an autograft is a graft of which the donor is also the recipient; a homograft , a graft of which the recipient is some other member of the donor’s species. ‘Orthotopic' grafts (not much will be said about any other) are grafts substituted for tissues or organs of the same kind as themselves: skin into gap in skin makes an orthotopic graft, or nerve into gap in nerve. The homograft reaction is the train of events that almost invariably causes a homograft of living tissue to be rejected by its host. Naturally it is most conspicuous in homografts of skin. If skin autografts and skin homografts are put side by side upon a rabbit, the autografts, after a period of minor reparative changes, return to something barely distinguishable from their original condition. The homografts heal into place and behave for some short time as if they too were autografts, but after 7 or 8 days they begin to get dark, hard and swollen; the corium is invaded by a population of mononuclear cells, the flow of blood and lymphatic drainage come to a standstill, and the epithelium begins to break up and lose its attachment to the connective tissue underneath. Within 3 or 4 days of the first signs of distress the homografts are destroyed completely. In due course their fibrous attachments are eaten through by the ingrowth of the host’s own epithelium and the grafts are sloughed away.