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In Vivo Expansion of Regulatory T Cells by Low-Dose Interleukin-2 Treatment
Increases Allograft Survival in Corneal Transplantation
#MMPMID26881788
Tahvildari M
; Omoto M
; Chen Y
; Emami-Naeini P
; Inomata T
; Dohlman TH
; Kaye AE
; Chauhan SK
; Dana R
Transplantation
2016[Mar]; 100
(3
): 525-32
PMID26881788
show ga
BACKGROUND: Corneal allograft survival dramatically decreases in hosts with
inflamed or vascularized recipient beds. We have previously shown that in
rejected corneal allografts regulatory T cells (Treg) demonstrate diminished
Foxp3 expression and immunoregulatory function. Treatment with low doses of IL-2
selectively expands Treg and has been proposed for the treatment of autoimmune
diseases. In this study, we investigated the effect of low-dose IL-2
administration on Treg function and corneal allograft survival. METHODS:
Allogeneic corneal transplantation was performed on inflamed host beds. Low-dose
systemic IL-2 was administered starting 3 days before grafting until 6 weeks
after transplantation. Frequencies of Treg and their immunosuppressive function
and antigen specificity were assessed using flow cytometry, in vitro
proliferation assays, and adoptive transfer experiments. Frequencies of effector
T cells (Teff) and graft infiltrating immune cells were measured at 2 weeks
posttransplantation. Long-term allograft survival was evaluated for up to 9 weeks
using Kaplan-Meier survival analysis. RESULTS: Treatment with low-dose IL-2
significantly increased frequencies of CD4CD25Foxp3 Treg and their
immunosuppressive function. It also suppressed alloimmune response as shown by
the decreased CD4 IFN? T cell frequencies and graft infiltration of CD45 and CD4
cells. Clinical evaluation of the grafts showed significant improvement in
long-term corneal allograft survival in the IL-2 treated group compared with
controls. CONCLUSIONS: Our study is the first to report that treatment with
low-dose IL-2 increases survival of corneal allografts. We propose that
IL-2-mediated Treg expansion can be an effective tool to prevent alloimmunity and
to improve long-term allograft survival in transplantation.
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