The effect of costimulatory and interleukin 2 receptor blockade on regulatory T cells in renal transplantation.
The effect of costimulatory and interleukin 2 receptor blockade on regulatory T cells in renal transplantation.
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DOI：
10.1111/j.1600-6143.2008.02377.x
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发表时间：
2008-10
期刊：
影响因子：
--
通讯作者：
Vincenti F
中科院分区：
文献类型：
--
作者：
Bluestone JA;Liu W;Yabu JM;Laszik ZG;Putnam A;Belingheri M;Gross DM;Townsend RM;Vincenti F
调节性T细胞（Treg）是免疫耐受的关键调节因子。IL-2和CD28-CD80/CD86信号对小鼠CD4+CD25+FOXP3+ Treg存活至关重要。然而，belatacept（第二代CTLA-4Ig）和basiliximab（一种抗cd25单克隆抗体）都是目前用于肾移植患者的免疫疗法。在本研究中，我们探讨了basiliximab和belatacept对急性排斥患者外周血treg的短期和长期以及肾活检的直接影响。我们报道，与钙调磷酸酶抑制剂（CNI）治疗组相比，belatacept/basiliximab联合治疗对循环treg没有长期影响。此外，与接受cni治疗的患者相比，接受belataccept治疗的患者在急性排斥反应期间的移植物活检中FOXP3+ T细胞数量显著增加。最后，在两个治疗组中，basiliximab似乎引起了循环中FOXP3+和FOXP3−CD25+ T细胞的短暂丢失，这提出了关于在促进耐受性的治疗方案中使用该疗法的重要问题。
Regulatory T cells (Treg) are critical regulators of immune tolerance. Both IL-2 and CD28-CD80/CD86 signaling are critical for CD4+CD25+FOXP3+ Treg survival in mice. Yet, both belatacept (a second-generation CTLA-4Ig) and basiliximab (an anti-CD25 monoclonal antibody) are among the arsenal of current immunotherapies being used in kidney transplant patients. In this study, we explored the direct effect of basiliximab and belatacept on the Tregs in peripheral blood both in the short term and long term and in kidney biopsies of patients with acute rejection. We report that the combined belatacept/basiliximab therapy has no long-term effect on circulating Tregs when compared to a calcineurin inhibitor (CNI)-treated group. Moreover, belatacept-treated patients had a significantly greater number of FOXP3+ T cells in graft biopsies during acute rejection as compared to CNI-treated patients. Finally, it appears that the basiliximab caused a transient loss of both FOXP3+ and FOXP3− CD25+ T cells in the circulation in both treatment groups raising important questions about the use of this therapy in tolerance promoting therapeutic protocols.
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CD127表达与FOXP3和人类CD4+ T Reg细胞的抑制功能成反比。
DOI：
10.1084/jem.20060772
发表时间：
2006-07-10
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
8.8
作者：
Bloom, D. D.;Chang, Z.;Knechtle, S. J.
通讯作者：
Knechtle, S. J.
DOI：
10.1073/pnas.0701171104
发表时间：
2007-04-10
影响因子：
11.1
作者：
You, Sylvaine;Leforban, Bertrand;Chatenoud, Lucienne
通讯作者：
Chatenoud, Lucienne
影响因子：
4.4
作者：
Tang, QZ;Henriksen, KJ;Bluestone, JA
通讯作者：
Bluestone, JA
影响因子：
6.2
作者：
ELLENHORN, JDI;WOODLE, ES;BLUESTONE, JA
通讯作者：
BLUESTONE, JA