Fine phenotypic and functional characterization of effector cluster of differentiation 8 positive T cells in human patients with primary biliary cirrhosis.
Fine phenotypic and functional characterization of effector cluster of differentiation 8 positive T cells in human patients with primary biliary cirrhosis.
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DOI：
10.1002/hep.24526
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发表时间：
2011-10
期刊：
影响因子：
13.5
通讯作者：
Gershwin, M. Eric
中科院分区：
文献类型：
--
作者：
Tsuda, Masanobu;Ambrosini, Yoko M.;Zhang, Weici;Yang, Guo-Xiang;Ando, Yugo;Rong, Guanghua;Tsuneyama, Koichi;Sumida, Kosuke;Shimoda, Shinji;Bowlus, Christopher L.;Leung, Patrick S. C.;He, Xiao-Song;Coppel, Ross L.;Ansari, Aftab A.;Lian, Zhe-Xiong;Gershwin, M. Eric
在原发性胆汁性肝硬化（PBC）中，患者对丙酮酸脱氢酶（PDC-E2） E2成分的高度限制性肽产生多谱系反应，包括自身抗体和自身反应性CD4+和CD8+ T细胞反应。最近来自小鼠模型的数据表明，肝脏浸润的CD8+细胞在PBC的胆道破坏中起关键作用。我们假设CD8+ T细胞的慢性抗原刺激改变效应记忆T细胞（TEM）的频率和功能，类似于慢性病毒感染，包括最终分化失败和对细胞凋亡的相对抗性。我们对132名受试者（包括76名PBC患者和56名对照）的CD8+ T细胞亚群进行了严格的表型分析，并报告了PBC患者PBMC中CD45ROhighCD57+CD8high但表达肠道归巢整合素α4β7的TEM细胞的频率更高。这些cd8高透射电镜细胞在TCR刺激后膜联蛋白V的表达降低。与TEM表型一致，CD45ROhighCD57+CD8high T细胞表达的颗粒酶a、颗粒酶B、穿孔素、CCR5和α4β7水平高于其他CD8high T细胞，而CCR7和CD28水平低于其他CD8high T细胞。此外，CD8+CD57+ T淋巴细胞在体外TCR刺激下产生的白细胞介素(IL)-5在PBC中增加。组织学上，PBC中CD8+CD57+ T细胞在门静脉周围聚集。此外，CD8+CD57+ T细胞对PDC-E2的MHC I类表位有特异性反应。总之，我们的数据表明，CD45ROhighCD57+CD8high T细胞是终末分化的细胞毒性TEM细胞的一个亚群，可能在胆道上皮细胞的进行性破坏中发挥关键作用。
In primary biliary cirrhosis (PBC), patients develop a multilineage response to a highly restricted peptide of the E2 component of pyruvate dehydrogenase (PDC-E2) involving autoantibody and autoreactive CD4+ and CD8+ T cell responses. Recent data from murine models have suggested that liver-infiltrating CD8+ cells play a critical role in biliary destruction in PBC. We hypothesized that chronic antigen stimulation of CD8+ T cells alters effector memory T cell (TEM) frequency and function similar to that seen with chronic viral infections including failure to terminally differentiate and relative resistance to apoptosis. We have rigorously phenotyped CD8+ T cell subpopulations from 132 subjects, including 76 patients with PBC and 56 controls, and report a higher frequency of TEM cells characterized as CD45ROhighCD57+CD8high but expressing the gut homing integrin α4β7 in PBMC of PBC. These CD8high TEM cells have reduced expression of annexin V after TCR stimulation. Consistent with a TEM phenotype, CD45ROhighCD57+CD8high T cells express higher levels of granzyme A, granzyme B, perforin, CCR5 and α4β7, and lower levels of CCR7 and CD28 than other CD8high T cells. Furthermore, interleukin (IL)-5 produced by CD8+CD57+ T lymphocytes upon in vitro TCR stimulation are increased in PBC. Histologically, CD8+CD57+ T cells accumulate around the portal area in PBC. Moreover, CD8+CD57+ T cells respond specifically to the MHC class I epitope of PDC-E2. In conclusion, our data demonstrate that CD45ROhighCD57+CD8high T cells are a subset of terminally differentiated cytotoxic TEM cells which could play a critical role in the progressive destruction of biliary epithelial cells.
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DOI：
10.1006/clin.1996.0129
发表时间：
1996-09-01
期刊：
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY
影响因子：
--
作者：
Krams, SM;Cao, S;Martinez, OM
通讯作者：
Martinez, OM
影响因子：
12.8
作者：
Lan RY;Salunga TL;Tsuneyama K;Lian ZX;Yang GX;Hsu W;Moritoki Y;Ansari AA;Kemper C;Price J;Atkinson JP;Coppel RL;Gershwin ME
通讯作者：
Gershwin ME
影响因子：
20.3
作者：
Lamy, T;Liu, JH;Loughran, TP
通讯作者：
Loughran, TP
影响因子：
5.5
作者：
Chattopadhyay, Pratip K.;Betts, Michael R.;De Rosa, Stephen C.
通讯作者：
De Rosa, Stephen C.
影响因子：
9.1
作者：
McNerlan, SE;Rea, IM;Morris, TCM
通讯作者：
Morris, TCM