Several component mechanisms of "central" (thymic) and "peripheral" tolerance in human organ transplant recipients are briefly discussed, in opposition to a more confined view limited to clonal depletion and exhaustion as proposed by Starzl (Transplantation 2004; 77(6): 926). Attention is directed to more than 40 years of experimental work in adult animal species dealing with immunoregulation. This work is in contradistinction to the simpler depletion/exhaustion explanation of Starzl (and Zinkernagel) regarding the potential of human organ transplant recipients to be significantly (or totally) withdrawn from continuous immunosuppression. Other observations are included touching on the roles of certain viral infections, the thymus, and the bone marrow in arriving at a state of "alloimmune homeostasis" in humans.
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