Variation in numbers of CD4+CD25highFOXP3+T cells with normal immuno-regulatory properties in long-term graft outcome

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Abstract
Chronic rejection (CR) is a major cause of long-term graft loss that would be avoided by the induction of tolerance. We previously showed that renal transplant patients with CR have lower numbers of peripheral CD4+CD25high T cells than operationally tolerant patients, patients with stable graft function and healthy volunteers (HV). We explored here the profile of CD4+CD25high blood T cells in these patients focusing on their expression of the regulatory T cells (Treg) gene Forkhead Box P3 (FOXP3) and their suppressive function. We show that CR is associated with a decreased number of CD4+CD25highFOXP3+T cells with normal regulatory profile, whereas graft acceptance is associated with CD4+CD25highFOXP3+T cell numbers similar to HVs. These data suggest that Treg numbers, rather than their intrinsic suppressive capacity, may contribute to determining the long-term fate of renal transplants.