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.
Subject(s)
Graft Rejection/prevention & control , Graft Survival , Immunosuppressive Agents/administration & dosage , Interleukin-2/administration & dosage , Sirolimus/administration & dosage , Skin Transplantation , Animals , Antineoplastic Agents/administration & dosage , Dose-Response Relationship, Drug , Drug Combinations , Flow Cytometry , Humans , Immunoenzyme Techniques , Lymphocyte Activation/drug effects , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Inbred DBA , Postoperative Complications , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/immunology , Transplantation Tolerance , Transplantation, HomologousABSTRACT
A concrete realisation of the "Geriatric assessment and management program" as described in the arrêté royal within a general hospital: definition of the geriatric patient, his detection, his follow-up and the transmission of patient information. The analysis of the first results indicates the importance of the biographic and socio-economics factors. The optimisation of an early screening and the communication between caregivers are key aspects to enhance the care of this patients.
