Acquired immunologic tolerance: with particular reference to transplantation

Abstract

The first unequivocally successful bone marrow cell transplantation in humans was recorded in 1968 by the University of Minnesota team of Robert A. Good (Gatti et al. Lancet 2: 1366-1369, 1968). This achievement was a direct extension of mouse models of acquired immunologic tolerance that were established 15 years earlier. In contrast, organ (i.e. kidney) transplantation was accomplished precociously in humans (in 1959) before demonstrating its feasibility in any experimental model and in the absence of a defensible immunologic rationale. Due to the striking differences between the outcomes with the two kinds of procedure, the mechanisms of organ engraftment were long thought to differ from the leukocyte chimerism-associated ones of bone marrow transplantation. This and other concepts of alloengraftment and acquired tolerance have changed over time. Current concepts and their clinical implications can be understood and discussed best from the perspective provided by the life and times of Bob Good.

Immunosuppressants: whatʼs new?

“…These findings support the concept that gradual reduction of immunosuppression is a key component of strategies to induce spontaneous tolerance in liver transplantation [24]. 'Tolerogenic' protocols Reports in adult LTx recipient have shown that operational tolerance can be achieved if there is a balance between donor cells and antidonor T cells [25 ].…”

Complications of right lobe living donor liver transplantation

“…After 3 weeks of low dose daily tacrolimus, right lobar LDLT was performed with continued minimum daily tacrolimus. The strategy in these 10 patients is described elsewhere [16]. …”

“…After complete removal of the recipient's diseased liver, the donor right lobe was transplanted to the vacated hepatic fossa, with technical variations that were dictated largely by anatomic variations in both the recipient and donor [14,15]. In addition to the hepatic allograft, 10 recipients during the last third of the experience (October 2005–October 2006) also were given an infusion of unmodified mononuclear cells obtained from the donor by leukopheresis [16]. …”

Five-year clinical effects of donor bone marrow cells infusions in kidney allograft recipients

“…3,4 This phenomenon may be a prerequisite for the maintenance of induced clonal deletion, a critical mechanism for acquired tolerance following transplantation. [5][6][7] Since the pioneering study by Starzl et al evaluating persistent systemic microchimerism in long-term allograft recipients, many clinical trials have been performed to confirm whether DBMC infusion can promote donor specific hyporesponsiveness thus improving long-term allograft survival. 4 However, only a limited number of trails (8)(9)(10)(11)(12) showed specific hyporesponsiveness and improved allograft survival in DBMC infused recipients compared with non-infused transplant recipients.…”