Operationally tolerant and minimally Immunosuppressed kidney recipients display strongly altered blood T-Cell clonal regulation

被引:64
作者
Brouard, S
Dupont, A
Giral, M
Louis, S
Lair, D
Braudeau, C
Degauque, N
Moizant, F
Pallier, A
Ruiz, C
Guillet, M
Laplaud, D
Soulillou, JP
机构
[1] CHU Hotel Dieu, INSERM, Unite Immunointervent Alloet Xenotransplantat 643, F-44093 Nantes 01, France
[2] CHU Hotel Dieu, Inst Transpalntat & Rech Transplantat, F-44093 Nantes 01, France
[3] CHU Hotel Dieu, Tcland SA, F-44093 Nantes 01, France
关键词
kidney transplantation; tolerance; T-cells; T-cell receptor;
D O I
10.1111/j.1600-6143.2004.00700.x
中图分类号
R61 [外科手术学];
学科分类号
摘要
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.
引用
收藏
页码:330 / 340
页数:11
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