Donor-specific tolerance in a murine model: the result of extra-thymic T cell deletion?

Abstract:

: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.

journal_name

Transpl Immunol

journal_title

Transplant immunology

authors

van Pel M,van Breugel DW,van Wijk M,Luypen S,Vingerhoed J,Roholl PJ,Boog CJ

doi

10.1016/S0966-3274(02)00157-0

subject

Has Abstract

pub_date

2003-07-01 00:00:00

pages

375-84

issue

3-4

eissn

0966-3274

issn

1878-5492

pii

S0966-3274(02)00157-0

journal_volume

11

pub_type

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