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PROPAGATION OF A UNIQUE V^σ1-BEARING V^σT CELLS CLONE WITHIN GRAFT INFILTRATES OF HUMAN LIVER TRANSPLANTATION TOLERANCE-IMMUNOPRIVILEGED LIVER SPECIFIC ?-

具有独特 V^σ1 的 V^σT 细胞克隆在移植物中的繁殖具有人类肝脏移植耐受性-免疫特权肝脏特异性？-

基本信息

批准号：
17591329
负责人：
KOSHIBA Takaaki
金额：
$ 2.24万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591329/
关键词：
liver tolerance 免疫制御移植ヒト γ6細胞

项目摘要

We reported that V^σ1bearing Y^σT cells (V^σ1 cells), which represent a minor subset of Y^σT cells in normal individuals, predominate over V^σ 2bearing Y^σT cells (V^σ2 cells) in peripheral blood of tolerant patients after liver transplantation (LTx). We further examined LTx tolerant patients for V^σ1 cells/V^σ2 cells (V^σ1/V^σ2) ratio and sequence in V^σ1 TCR chains in graft infiltrates. To elucidate whether V^σ1 cells are responsible for immunoprivilege of LTx, highly immunogenic intestinal Tx (ITx) was studied in addition. Method Protocol biopsy was performed in patients whose grafts were functioning well despite the absence of or minimum immunosuppression after LTx (N= 18) and intestinal Tx (ITx) (N=3)(Gr-To1). Total RNA was extracted to synthesize cDNA. V^σ1 and V^σ2 gene expressions were quantified by real-time PCR, and CDR3 sequence in V^σ1 TCR chains was analyzed. The results were compared to those of chronically rejecting grafts (Gr-CR N=9) and normal liver (Gr-Nor N=6) in LTx and native intestines of the patients (Gr-Nat N=2) in ITx. Results LTx ; V^σ1/V^σ2 ratio was the highest in Gr-Tol, compared to those in Gr-CR and Gr-Nor (p<0.05). Sequences of V^σ1 in Gr-Tol were shifted towards mono-/oligo-clonal pattern, while polyclonal in Gr-CR. One dominant sequence was observed in 8 out of 9 tolerant patients but identical sequence was not seen in Gr-CR. ITx ; Unlike LTx, there was no difference between V^σ1/V^σ2 ratio of Gr-Tol and Gr-Nat. Neither mono-/oligo-clonal shift of V^σ1 sequence nor any common sequence was observed among patients in Gr-Tol. Conclusion A unique V^σ1T cell clone propagated within tolerant liver graft but not tolerant intestinal graft. We hypothesize that this propagation is liver-antigen-selected and associated with a mechanism of immunoprivilege of liver Tx.

我们报道了在肝移植（LTx）后耐受患者外周血中，携带V^σ 1的Y ^σ T细胞（V^σ1细胞）占优势，而携带V^σ 2的Y^σT细胞（V^σ2细胞）占优势。我们进一步检查了LTx耐受患者的移植物浸润中V ^σ1 TCR链中的V^σ1细胞/V^σ2细胞（V^σ1/V^σ2）比率和序列。为了阐明V^σ1细胞是否负责LTx的免疫豁免，另外研究了高免疫原性肠Tx（ITx）。方法对18例LTx（N= 18）和3例ITx（N=3）术后移植物功能良好的患者进行常规活检（Gr-To 1）。提取总RNA合成cDNA。通过实时PCR定量V^σ1和V^σ2基因表达，并分析V^σ1 TCR链中的CDR 3序列。将结果与LTx中的慢性排斥移植物（Gr-CR N=9）和正常肝脏（Gr-Nor N=6）以及ITx中的患者的自体肠（Gr-Nat N=2）的结果进行比较。结果Gr-Tol组LTx ; V^σ1/V^σ2比值最高，与Gr-CR组和Gr-Nor组比较差异有统计学意义（p<0.05）。在Gr-Tol中V^σ1序列向单克隆/寡克隆模式转变，而在Gr-CR中则向多克隆模式转变。在9例耐受患者中有8例观察到一个显性序列，而在Gr-CR中未观察到相同的序列。ITx ;与LTx不同，Gr-Tol和Gr-Nat的V^σ1/V^σ2比值无差异，在Gr-Tol中未观察到V^σ1序列的单克隆/寡克隆移位，也未观察到任何共同序列。结论在耐受性肝移植物中存在一种独特的V^σ 1 T细胞克隆，但在耐受性肠移植物中不存在。我们假设这种传播是肝抗原选择的，并与肝Tx的免疫豁免机制相关。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Proinflammatory and antiinflamnatory cytokine production duringi schemia-reperfusion injury in a case of identical twin living donor liver transplantation using no immunosuppression.

在不使用免疫抑制的同卵双胞胎活体肝移植病例中，缺血再灌注损伤期间促炎和抗炎细胞因子的产生。

DOI：
发表时间：
2005
期刊：
Transplant Proc 37
影响因子：
0
作者：
Zhao X;Koshiba T;Fujimoto Y;Pirenne J;Yoshizawa A;Ito T;Kamei H;Uehara K;Ogawa K;Uryuhara K;Takada Y;Tanaka K.
通讯作者：
Tanaka K.

Clinical, immunological, and pathological aspects of operational tolerance after pediatric living-donor liver transplantation