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Consequently, it was assumed for many years that success with organ and bone marrow transplantation involved fundamentally different mechanisms. With the discovery in 1992 of small numbers of donor leukocytes in the tissues or blood of long-surviving organ recipients (microchimerism), we concluded that organ engraftment was a form of leukocyte chimerism-dependent partial tolerance. In this initially controversial paradigm, alloengraftment after both kinds of transplantation is the product of a double immune reaction in which responses, each to the other, of coexisting donor and recipient immune systems results in variable reciprocal clonal exhaustion, followed by peripheral clonal deletion. It was proposed with Rolf Zinkernagel that the individual alloresponses are the equivalent of the MHC-restricted T cell recognition of, and host response to, intracellular parasites and that the mechanisms of immune responsiveness, or nonresponsiveness, are governed by the migration and localization of the respective antigens. Elucidation of the mechanisms of nonresponsiveness (clonal exhaustion-deletion and immune ignorance) and their regulation removed much of the historical mystique of transplantation. The insight was then applied to improve the timing and dosage of immunosuppression of current human transplant recipients.<\/jats:p>","DOI":"10.1073\/pnas.0404829101","type":"journal-article","created":{"date-parts":[[2004,8,19]],"date-time":"2004-08-19T23:02:35Z","timestamp":1092956555000},"page":"14607-14614","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":118,"title":["Chimerism and tolerance in transplantation"],"prefix":"10.1073","volume":"101","author":[{"given":"Thomas E.","family":"Starzl","sequence":"first","affiliation":[{"name":"Transplantation Institute, University of Pittsburgh Medical Center, 3459 Fifth Avenue, Pittsburgh, PA 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2004,10,5]]},"reference":[{"key":"e_1_3_1_1_2","first-page":"299","volume":"77","year":"1943","unstructured":"Gibson, T. & Medawar, P. B. (1943) J. 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