Table of Contents Author Guidelines Submit a Manuscript
Journal of Transplantation
Volume 2011, Article ID 760319, 4 pages
http://dx.doi.org/10.1155/2011/760319
Research Article

Transplantation Tolerance Induced in Humans at the Fetal or the Neonatal Stage

1Claude Bernard University and Hospices Civils de Lyon, France
2Transplant Unit, Pav. P., Hôpital Ed. Herriot, 69437 Lyon Cedex 3, France

Received 2 March 2011; Accepted 6 May 2011

Academic Editor: Hargovind L. Trivedi

Copyright © 2011 Jean-Louis Touraine and Kamel Sanhadji. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Patients transplanted with HLA-mismatched stem cells from fetal livers develop transplantation tolerance to donor antigens. Engraftment needs no conditioning regimen prior to transplantation in neonates with severe combined immunodeficiency disease or in human fetal patients having not yet developed any immune maturity, especially T-cell differentiation. The chimeric patients have donor-derived T lymphocytes which progressively demonstrate positive interactions with other host cells. They also can be shown to be tolerant toward both host and donor antigens. The latter tolerance relies upon clonal deletion from the T-cell repertoire, and it results from the contact between thymocytes of donor origin and dendritic cells or macrophages also deriving from donor stem cells. The former tolerance does not imply clonal deletion of T-cells with host reactivity. Numerous T-cells recognizing the allogeneic, host-type antigens are identified in these patients, but these cells are anergized, following interaction with epithelial cells of the host thymus. Induction of transplantation tolerance at the fetal stage requires minimal engraftment only; in the future it will be possible to further amplify the clinical benefit, using additional cell transplants after birth.