Donor cell chimerism permitted by immunosuppressive drugs: a new view of organ transplantation

Abstract

One line of thought in organ transplantation feels that immunosuppressive drugs can lead to tolerance induction by allowing a previously unrecognized common mechanism of cell migration and microchimerism to occur, persist, and in some cases, become drug independent. It has been recognized that there is a spectrum of susceptibility of different organs to cellular rejection and that the variable ability of these organs to induce donor-specific nonreactivity reflects their comparative content of migratory leukocytes. Here, Thomas Starzl and colleagues discuss how many of the enigmas of transplantation immunology can be explained by this chimerism.

Fig. 1

The mutual engagement of migratory immunocytes from the graft and the recipient following organ transplantation under potent pharmacological immunosuppression. GVH: graft versus host; HVG: host versus graft.

Fig. 2

The characteristic cycle of immunological confrontation and recovery after organ transplantation (in this case kidney) that has dictated the use of immunosuppressive drugs for the last 30 years. Following a period of good postoperative renal function, rejection 2-1/2 weeks after transplantation (Tx) was correlated with a fall in creatinine clearance (Ccr), a rise in blood urea nitrogen (BUN) and an increase in circulating white blood cells (WBC). The adverse findings were reversed with prednisone, which was later discontinued along with a reduction of maintenance azathioprine. The kidney allograft in this 23 year old man functioned continuously from April 1963 until death from a myocardial infarction in 1990. (Adapted from Starzl, T.E., Experience In Renal Transplantation, W.B. Saunders Company, Philadelphia, PA, 1964, p. 167.)

Fig. 3

The donor–recipient leukocyte interaction shown in Fig. 1 is a buffer against rejection on one hand and GVHD on the other. Veto and suppressor cells are postulated to be the result of the interaction. Rx: iatrogenic immunosuppression.