Lymphocytes Selected in Allogeneic Thymic Epithelium Mediate Dominant Tolerance Toward Tissue Grafts of the Thymic Epithelium Haplotype

Athymic mice grafted at birth with allogeneic thymic epithelium (TE) from day 10 embryos before hematopoietic cell colonization reconstitute normal numbers of T cells and exhibit full life-long tolerance to skin grafts of the TE haplotype. Intravenous transfers of splenic cells, from these animals t...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1995-08, Vol.92 (16), p.7555-7559
Main Authors: Modigliani, Yves, Thomas-Vaslin, Veronique, Bandeira, Antonio, Coltey, Monique, Le Douarin, Nicole M., Coutinho, Antonio, Salaun, Josselyne
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
Antigens
Biochemistry
Chimera
Chimeras
Epithelial Cells
Epithelium - immunology
Epithelium - transplantation
Exercise tolerance
Graft Rejection
Haplotypes
Immune Tolerance
Immunity (Disease)
Immunotherapy, Adoptive
Mice
Mice, Inbred BALB C
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Nude
Mice, Transgenic
Rodents
Skin grafts
T lymphocytes
T-Lymphocytes - immunology
T-Lymphocytes - transplantation
Thymus Gland - cytology
Thymus Gland - immunology
Thymus Gland - transplantation
Tissue grafting
Transplantation tolerance
Transplantation, Homologous
Transplantation, Isogeneic
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Summary:Athymic mice grafted at birth with allogeneic thymic epithelium (TE) from day 10 embryos before hematopoietic cell colonization reconstitute normal numbers of T cells and exhibit full life-long tolerance to skin grafts of the TE haplotype. Intravenous transfers of splenic cells, from these animals to adult syngeneic athymic recipients, reconstitute T-cell compartments and the ability to reject third-party skin grafts. The transfer of specific tolerance to skin grafts of the TE donor strain, however, is not observed in all reconstituted recipients, and the fraction of nontolerant recipients increases with decreasing numbers of cells transferred. Furthermore, transfers of high numbers of total or CD4+T cells from TE chimeras to T-cell receptor-anti-H-Y antigen transgenic immunocompetent syngeneic hosts specifically hinder the rejection of skin grafts of the TE haplotype that normally occurs in such recipients. These observations demonstrate (i) that mice tolerized by allogeneic TE and bearing healthy skin grafts harbor peripheral immunocompetent T cells capable of rejecting this very same graft; and (ii) that TE selects for regulatory T cells that can inhibit effector activities of graft-reactive cells.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.92.16.7555