Operationally tolerant and minimally immunosuppressed kidney recipients display strongly altered blood T-cell clonal regulation.
Most kidney transplant recipients who discontinue immunosuppression reject their graft. Nevertheless, a small number do not, suggesting that allogeneic tolerance state (referred to operational tolerance) is achievable in humans. So far, however, the rarity of such patients has limited their study. Because operational tolerance could be linked to anergy, ignorance or to an active regulatory mechanism, we analyzed the blood T-cell repertoire usage of these patients. We report on comparison of T-cell selection in drug-free operationally tolerant kidney recipients (or with minimal immunosuppression), recipients with stable graft function, chronic rejection and healthy individuals. The blood T cells of operationally tolerant patients display two major characteristics: an unexpected strongly altered T-cell receptor (TCR) Vbeta usage and high TCR transcript accumulation in selected T cells. The cytokine transcriptional patterns of sorted T cells with altered TCR usage show no accumulation of cytokine transcripts (IL10, IL2, IL13, IFN-gamma), suggesting a state of hyporesponsiveness in these patients. Identification of such a potential surrogate pattern of operational tolerance in transplant recipients under life-long immunosuppression may provide a new basis and rationale for exploration of tolerance state. However, these data obtained in a limited number of patients require further confirmation on larger series.
Brouard
Sophie
S
Institut National de la Santé Et de la Recherche Médicale, Unité 643: Immunointervention dans les Allo-et Xénotransplantations and Institut de Transplantation Et de Recherche en Transplantation, CHU Hôtel-Dieu, 44093 Nantes Cedex 01, France.
Dupont
Alexandre
A
Giral
Magali
M
Louis
Stéphanie
S
Lair
David
D
Braudeau
Cécile
C
Degauque
Nicolas
N
Moizant
Frédérique
F
Pallier
Annaick
A
Ruiz
Catherine
C
Guillet
Marina
M
Laplaud
David
D
Soulillou
Jean-Paul
JP
D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016030:Kidney Transplantation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors
D007166:Immunosuppressive Agents; D011948:Receptors, Antigen, T-Cell