Variation in numbers of CD4+CD25highFOXP3+ T cells with normal immuno-regulatory properties in long-term graft outcome.
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(+)CD25(high) T cells than operationally tolerant patients, patients with stable graft function and healthy volunteers (HV). We explored here the profile of CD4(+)CD25(high) 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(+)CD25(high)FOXP3(+)T cells with normal regulatory profile, whereas graft acceptance is associated with CD4(+)CD25(high)FOXP3(+)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.
Braudeau
Cécile
C
INSERM, U643, Nantes, F44000, France.
Racape
Maud
M
Giral
Magali
M
Louis
Stéphanie
S
Moreau
Anne
A
Berthelot
Laureline
L
Heslan
Michèle
M
Ashton-Chess
Joanna
J
Soulillou
Jean-Paul
JP
Brouard
Sophie
S
D000328:Adult; D000368:Aged; D015704:CD4 Antigens / Q000276:immunology*; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000276:immunology*; D006084:Graft Rejection / Q000097:blood / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007108:Immune Tolerance; D007111:Immunity, Cellular / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit