Some murine allogeneic organ and tumor grafts which are not rejected: The importance of local factors

Abstract

The experiments which I was privileged to do with Peter Medawar in his small laboratory at University College mainly concerned the grafting of adrenal cortical tissue in mice. They followed his characteristically simple and direct design and were conducted almost entirely with whole, living animals. The newly discovered phenomenon of acquired immunological tolerance was employed in some experiments to allow survival of adrenal grafts which were then summarily dispatched as tolerance was abolished. In other experiments immunologically privileged sites were seen to be intriguingly successful in allowing adrenal transplant survival (1). In some later unpublished work using a system of parathyroid transplants in rats, which I had worked out with Ruben Gittes (2), it was found that prompt rejection of surviving grafts in several privileged sites could be provoked with skin grafts of donor origin. Ever since those happy days in London I have retained a strong impression that the intimate nature of the contact between graft and host can be extremely important to the fate of the graft, and that quite often the survival of a graft hangs in a delicate balance, a balance which can be influenced by a number of factors only some of which are now understood. We have recently been studying some examples of transplants which survive in mice without any immunosuppressive treatment in spite of well-defined histoincompatibility between their congenic donors and recipients. In particular we have concentrated upon a strain combination in which the difference between donor and recipient is determined at the K end of the H-2 region. Donors are of the BlO.D2 strain and recipients are (C57BL/6 X A/J)F, hybrids, termed B6AF,. I will concentrate particularly on two examples in which transplants survive in the face of this incompatibility, but they do so for quite different reasons. In both cases local factors associated with the transplant seem to be important. The first example involves kidney transplants transferred between mice with primary vascular union