Donor-specific tolerance in a murine model: the result of extra-thymic T cell deletion?
| Autor: | Melissa van Pel, Jose Vingerhoed, Margot van Wijk, Danielle W.J.G. van Breugel, Claire J.P. Boog, Paul J.M. Roholl, Sacco Luypen |
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| Rok vydání: | 2003 |
| Předmět: |
Male
Time Factors Transplantation Conditioning T-Lymphocytes T cell Immunology Clonal Deletion Thymus Gland Biology Clonal deletion Mice Intestine Small Immune Tolerance medicine Animals Transplantation Homologous Immunology and Allergy Cytotoxic T cell Antigen-presenting cell Bone Marrow Transplantation Mice Inbred BALB C Transplantation Clonal anergy Chimera Skin Transplantation Thymectomy Molecular biology Tolerance induction medicine.anatomical_structure T cell selection Transplantation Tolerance |
| Zdroj: | Transplant Immunology. 11:375-384 |
| ISSN: | 0966-3274 |
| DOI: | 10.1016/s0966-3274(02)00157-0 |
| Popis: | Previously, we established a murine model, that involves the engraftment of fully allogeneic T cell depleted donor bone marrow cells in sublethally irradiated and single dose anti-CD3 treated recipient mice. These mice developed permanent stable multilineage mixed chimerism and donor-specific tolerance without graft-versus-host disease. Recently, we have shown that donor-specific tolerance is not induced and/or maintained by clonal anergy, neither by a Th1/Th2 shift, nor by suppressor or other regulatory processes. In the present study, we investigated whether clonal deletion plays a role in tolerance induction in our model. We studied the kinetics of TCRVbeta8(+) T cells in BALB/c (H-2L(d+))--dm2 (H-2L(d-)) chimeras, in which combination of mouse strains TCRVbeta8 predominates the anti-donor response. We found that TCRVbeta8(+) T cells were specifically deleted. To our surprise, this deletion was also found in mixed chimeras, thymectomized prior to the conditioning regimen. We conclude that clonal deletion plays a role in the establishment and maintenance of donor-specific tolerance, and that the thymus is not required for this process. In addition, confocal laser-scanning microscopy clearly showed the presence of abundant amounts of donor T cells and some donor antigen presenting cells in the small intestine in thymectomized chimeras and not in other organs, suggesting that T cell selection might take place in this organ in the absence of the thymus. |
| Databáze: | OpenAIRE |
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