Format

Send to

Choose Destination
Am J Transplant. 2014 Dec;14(12):2874-82. doi: 10.1111/ajt.12944. Epub 2014 Nov 13.

Administration of low doses of IL-2 combined to rapamycin promotes allogeneic skin graft survival in mice.

Author information

1
Faculté de Médecine, Université Paris-Est Créteil, Créteil, France; Institut Mondor de Recherche Biomédicale (IMRB), INSERM U 955, Créteil, France; AP-HP, Groupe Hospitalier Henri-Mondor Albert-Chenevier, CIC-BT-504, Créteil, France.

Abstract

Human CD4(+) CD25(+) FoxP3(+) regulatory T cells (Tregs) prevent allogeneic graft rejection by inhibiting T cell activation, as has been shown in mouse models. Recently, low-dose IL-2 administration was shown to specifically activate Tregs but not pathogenic conventional T cells, leading to resolution of type 1 diabetes in nonobese diabetic mice. We therefore tested the ability of low-dose IL-2 to prevent allogeneic skin graft rejection. We found that while IL-2 alone was inefficient in preventing rejection, combined with rapamycin, IL-2 treatment promoted skin graft survival both in minor disparate and semi-allogeneic skin graft combinations. Tregs are activated by this combined treatment while conventional CD4(+) cell expansion and activation are markedly inhibited. Co-administration of anti-CD25 antibodies dramatically reduces the effect of the IL-2/rapamycin treatment, strongly supporting a central role for Treg activation. Thus, we provide the first preclinical data showing that low-dose IL-2 combined with rapamycin can significantly delay transplant rejection in mice. These findings may form the rational for clinical evaluation of this novel approach for the prevention of transplant rejection.

KEYWORDS:

Basic (laboratory) research; alloantigen; graft survival; immune modulation; immune regulation; immunobiology; immunosuppression; murine; tissue (nonvascularized); tolerance; translational research; transplantation

PMID:
25394722
DOI:
10.1111/ajt.12944
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center