IL-2-Mediated In Vivo Expansion of Regulatory T Cells Combined with CD154-CD40 Co-Stimulation Blockade but Not CTLA-4 Ig Prolongs Allograft Survival in Naive and Sensitized Mice.

ABSTRACT: In recent years, regulatory T cells (Treg)-based immunotherapy has emerged as a promising strategy to promote operational tolerance after solid organ transplantation (SOT). However, a main hurdle for the therapeutic use of Treg in transplantation is their low frequency, particularly in non-lymphopenic hosts. We aimed to expand Treg directly in vivo and determine their efficacy in promoting donor-specific tolerance, using a stringent experimental model. Administration of the IL-2/JES6-1 immune complex at the time of transplantation resulted in significant expansion of donor-specific Treg, which suppressed alloreactive T cells. IL-2-mediated Treg expansion in combination with short-term CD154-CD40 co-stimulation blockade, but not CTLA-4 Ig or rapamycin, led to tolerance to MHC-mismatc

SUBMITTER: Govender L 

PROVIDER: S-EPMC5399033 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature