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© Research
Publication : European journal of immunology

Regulatory T cells in thymic epithelium-induced tolerance. I. Suppression of mature peripheral non-tolerant T cells

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in European journal of immunology - 01 Sep 1995

Modigliani Y, Pereira P, Thomas-Vaslin V, Salaün J, Burlen-Defranoux O, Coutinho A, Le Douarin N, Bandeira A

Link to Pubmed [PMID] – 7589127

Eur. J. Immunol. 1995 Sep;25(9):2563-71

Athymic mice grafted at birth with allogeneic thymic epithelium (TE) display life-long tolerance to tissue grafts of the TE donor strain, in spite of harboring peripheral T cells capable of rejecting those grafts. Tolerance is maintained in these chimeras by TE-specific regulatory CD4 T cells. We presently address the quantification and the mechanisms of this dominant tolerance process. C57BL/6 mice containing variable but defined numbers of peripheral, resident T cells received cell transfers of graded numbers of peripheral T cells from B6(BALB E10) chimeras (C57BL/6 nude mice grafted with TE from 10-day-old BALB/c embryos), resulting in a series of animals containing a wide range of donor (tolerant) versus host (non-tolerant) T cell chimerism. Increasing the relative representation of donor T cells results in a progressive delay in the rejection of BALB/c skin grafts, life-long tolerance being achieved at a ratio of tolerant and non-tolerant T cell populations of 1. In recipients displaying full tolerance, graft-reactive non-tolerant T cells were not deleted, anergized or committed to noninflammatory functions. Thus, sorted host T cells from tolerant recipients readily rejected BALB/c skin grafts upon transfer to immunodeficient animals. Finally, measurements of “helper” and inflammatory activities, as well as interleukin-4 and interferon-gamma production, failed to discriminate between T cell populations from tolerant and non-tolerant animals after specific in vitro stimulation. We conclude that: (a) TE-selected regulatory T cells can suppress, in a quantitative manner, in vivo T cell responses against major and minor histocompatibility antigens expressed by the TE and, (b) this suppressive activity neither inactivates mature non-tolerant T cells, nor does it seem to drive their differentiation along noninflammatory pathways.

http://www.ncbi.nlm.nih.gov/pubmed/7589127