Chimerism in organ transplantation: conflicting experiments and clinical observations

The concepts of chimerism has influenced our thinking about tolerance and rejection of organs and tissues since the beginning of modern transplantation. In macrochimerism, persisting donor-specific cells are easily detectable by flow cytometry at levels of several to 100%, usually after transient lymphoablation and bone marrow (or other cell) transplantation. Microchimerism refers to a state in which donor cells persist at low levels (1 cell per 10(4) or 10(5) or less), frequently detectable by molecular techniques and usually consisting of class II dendritic cells. Although macrochimerism is frequently associated with donor-specific tolerance in many experimental animals and people, instances occur in which macrochimerism can be produced, but tolerance is not achieved. Also, in large animal models, macrochimerism and associated tolerance can be produced but macrochimerism can then disappear, yet tolerance persists. Clinically, states of microchimerism can exist, but rejection still occurs. Also, persisting microchimerism does not necessarily correlate with clinical tolerance or the ability to wean from or reduce immunosuppressive drugs. Recent experiments in several rodents using bone marrow to induce macrochimerism and tolerance have shown that establishment of the macrochimeric state does not necessarily produce tolerance. The presence of class II positive cells in the donor bone marrow inoculum is essential for tolerance induction in these models.