Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Chimerism and tolerance in transplantation

Starzl, Thomas E (2004) Chimerism and tolerance in transplantation. Proceedings of the National Academy of Sciences, 101 (suppl_). 14607 - 14614. ISSN 0027-8424

Accepted Version
Available under License : See the attached license file.

Download (1MB) | Preview
[img] Plain Text (licence)
Available under License : See the attached license file.

Download (1kB)


<jats:p>Studies in experimental models (1953–1956) demonstrated that acquired donor-specific allotolerance in immunologically immature or irradiated animals is strongly associated with donor leukocyte chimerism. Bone marrow transplantation in immune-deficient or cytoablated human recipients was a logical extension (1968). In contrast, clinical (1959) and then experimental organ transplantation was systematically accomplished in the apparent absence of leukocyte chimerism. 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>


Social Networking:
Share |


Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Starzl, Thomas Etes11@pitt.eduTES11
Centers: Other Centers, Institutes, Offices, or Units > Thomas E. Starzl Transplantation Institute
Date: 5 October 2004
Date Type: Publication
Journal or Publication Title: Proceedings of the National Academy of Sciences
Volume: 101
Number: suppl_
Publisher: Proceedings of the National Academy of Sciences
Page Range: 14607 - 14614
DOI or Unique Handle: 10.1073/pnas.0404829101
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0027-8424
Other ID: uls-drl:31735062121128, Starzl CV No. 2200
Date Deposited: 08 Apr 2010 17:37
Last Modified: 20 Mar 2022 14:55


Monthly Views for the past 3 years

Plum Analytics

Actions (login required)

View Item View Item