title: Operationally tolerant and minimally immunosuppressed kidney recipients display strongly altered blood T-cell clonal regulation.
abstract: 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.
authors.affiliation: 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.
authors.forename: Sophie
authors.initials: S
authors.lastname: Brouard
authors.forename: Alexandre
authors.initials: A
authors.lastname: Dupont
authors.forename: Magali
authors.initials: M
authors.lastname: Giral
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Louis
authors.forename: David
authors.initials: D
authors.lastname: Lair
authors.forename: Cécile
authors.initials: C
authors.lastname: Braudeau
authors.forename: Nicolas
authors.initials: N
authors.lastname: Degauque
authors.forename: Frédérique
authors.initials: F
authors.lastname: Moizant
authors.forename: Annaick
authors.initials: A
authors.lastname: Pallier
authors.forename: Catherine
authors.initials: C
authors.lastname: Ruiz
authors.forename: Marina
authors.initials: M
authors.lastname: Guillet
authors.forename: David
authors.initials: D
authors.lastname: Laplaud
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Soulillou
mesh_terms: 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
chemical_list: D007166:Immunosuppressive Agents; D011948:Receptors, Antigen, T-Cell