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  • Title: Development of CD25- regulatory T cells following heart transplantation: evidence for transfer of long-term survival.
    Author: Degauque N, Lair D, Braudeau C, Haspot F, Sébille F, Dupont A, Merieau E, Brouard S, Soulillou JP.
    Journal: Eur J Immunol; 2007 Jan; 37(1):147-56. PubMed ID: 17171754.
    Abstract:
    Donor-specific heart allograft acceptance can be induced in the MHC-mismatched LEW.1 W to LEW.1A rat by donor-specific transfusions. Whereas the induction phase of tolerance has been studied in detail, its maintenance remained poorly understood. Here, we performed a side-by-side comparison of CD25+ and CD25- splenic T cells of 100-day tolerant rats. Administration of CD25- T cells from tolerant rats to sublethally irradiated recipients transferred long-term graft survival. These CD25- T cells displayed a decreased donor-specific response in the mixed lymphocyte reaction and presented suppressive activity. These CD25- T cells accumulated IFN-gamma, IL-10 and Foxp3 transcripts. The in vitro suppressive activity of CD25- T cells required both cell contact and soluble factors (IL-10 and IFN-gamma). The CD25+ T cells from tolerant rats did not show any modification of their regulatory properties. We show that splenic CD25- T cells of tolerant rats contribute to the maintenance of tolerance following the transplantation. Our data show that regulatory T cells are not restricted to the CD4+ CD25+ T cell subset and provide new insights on the mechanisms of tolerance to allograft following donor cell priming.
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