title: Development of CD25- regulatory T cells following heart transplantation: evidence for transfer of long-term survival.
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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Nantes, UMR 643, Nantes, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Degauque
authors.forename: David
authors.initials: D
authors.lastname: Lair
authors.forename: Cécile
authors.initials: C
authors.lastname: Braudeau
authors.forename: Fabienne
authors.initials: F
authors.lastname: Haspot
authors.forename: Fabien
authors.initials: F
authors.lastname: Sébille
authors.forename: Alexandre
authors.initials: A
authors.lastname: Dupont
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Merieau
authors.forename: Sophie
authors.initials: S
authors.lastname: Brouard
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Soulillou
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D016207:Cytokines / Q000502:physiology; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D007108:Immune Tolerance; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
chemical_list: D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit