Transplantation milestones. Viewed with one- and two-way paradigms of tolerance

Abstract

TEN YEARS ago in this journal's Landmark Article series of reproduced historical publications, the remarkable impact was described 1 of the 1956 report in JAMA by Merrill et al 2 of an identical twin renal transplantation. The operation was performed in December 1954, by Joseph E. Murray (Nobel Laureate, 1990) and his associates at the Peter Bent Brigham Hospital, Boston, Mass. By avoiding problems with rejection, such cases symbolized what might someday be accomplished if the immunologic reaction could be controlled. Then, on January 24, 1959, the barrier posed by genetic nonidentity was breached for the kidneys with a successful fraternal twin transplantation 3 by the same team.

Variable Chimerism, Graft-Versus-Host Disease, and Tolerance After Different Kinds of Cell and Whole Organ Transplantation From Lewis to Brown Norway Rats

“…We have proposed that the interaction, each with the other, of the 2 coexisting cell popUlations after either isolated or leukocyte-augmented organ transplantation is the fundamental explanation of organ allograft acceptance and of transplantation tolerance generally (1)(2)(3)(4)(5)(78)(79)(80)(81)(82). A similar reciprocal reaction hypothesis to explain acquired tolerance after splenocyte and bone malTOW transplantation was advanced by Simonsen 35 years ago (83,84) and supported by Michie, Zeiss, and Woodruff (85).…”

“…However, we have frequently emphasized (1,2,5,82,142) that chimerism is in no sense a substitute for the immunosuppression upon which the donor leukocyte engraftment and the eventual stability of chimerism depends-especially if the MHC barrier is a difficult one or if the chimeric population is small. In humans, the dividend of stable chimerism and its corollary of drug-free tolerance are expected to take years rather than the days or weeks of our rodent experiments.…”

Tolerance for organ recipients: A clash of paradigms

“…16 These findings unified the immunology of the 2 kinds of transplantation. 17 Moreover, only 2 mechanisms involving the mobile leukocytes were needed to explain how an allograft could avoid rejection. 18 One mechanism was immune ignorance: i.e., failure of the immune system to recognize the presence of donor leukocytes that failed to reach host lymphoid organs.…”

“…This is the usual outcome after clinical organ transplantation. 14,15,17,18 It follows that the completeness of tolerance short of the drug-free state can be inferred from the amount of immunosuppression needed to maintain graft stability. 18,24,25 None of the patients of Donckier et al 1 had macrochimerism.…”

Dendritic cells and tolerance induction

“…A recent clue to the mechanisms of tolerogenicity exerted by hepatic allografts are reports that leucocytes of donor origin, of which DC feature prominently, can be identified at distant sites of long-surviving successful graft recipients [11,12]. This has given rise to the idea that donor-derived cells (donor leucocyte microchimaerism) may be a cause rather than a consequence of graft survival, and that evolving mutual suppression of donor-recipient leucocyte interaction may be the basis of transplantation tolerance (the two-way paradigm) [41][42][43].…”