Hepatocyte-induced CD4(+) T cell alloresponse is associated with major histocompatibility complex class II up-regulation on hepatocytes and suppressible by regulatory T cells

DeTemple Daphne E.; Oldhafer Felix; Falk Christine S.; Chen-Wacker Chen; Figueiredo Constanca; Kleine Moritz; Ramackers Wolf; Timrott Kai; Lehner Frank; Klempnauer Juergen; Bock Michael; Vondran Florian W. R.

首页> 外文期刊>Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society >Hepatocyte-induced CD4(+) T cell alloresponse is associated with major histocompatibility complex class II up-regulation on hepatocytes and suppressible by regulatory T cells

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Hepatocyte-induced CD4(+) T cell alloresponse is associated with major histocompatibility complex class II up-regulation on hepatocytes and suppressible by regulatory T cells

机译：肝细胞诱导的CD4（+）T细胞反应与肝细胞的主要组织相容性复合体II升高，并通过调节T细胞抑制

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Hepatocyte transplantation is a promising therapeutic approach for various liver diseases. Despite the liver's tolerogenic potential, early immune-mediated loss of transplanted cells is observed, and longterm acceptance has not been achieved yet. Patients deemed tolerant after liver transplantation presented an increased frequency of regulatory T cells (Tregs), which therefore also might enable reduction of posttransplant cell loss and enhance longterm allograft acceptance. We hence characterized hepatocyte-induced immune reactions and evaluated the immunomodulatory potential of Tregs applying mixed lymphocyte cultures and mixed lymphocyte hepatocyte cultures. These were set up using peripheral blood mononuclear cells and primary human hepatocytes, respectively. Polyclonally expanded CD4(+)CD25(high)CD127(low) Tregs were added to cocultures in single-/trans-well setups with/without supplementation of anti-interferon (IFN) antibodies. Hepatocyte-induced alloresponses were then analyzed by multicolor flow cytometry. Measurements indicated that T cell response upon stimulation was associated with IFN-induced major histocompatibility complex (MHC) class II up-regulation on hepatocytes and mediated by CD4(+) T cells. An indirect route of antigen presentation could be ruled out by use of fragmented hepatocytes and culture supernatants of hepatocytes. Allospecific proliferation was accompanied by inflammatory cytokine secretion. CD8(+) T cells showed early up-regulation of CD69 despite lack of cell proliferation in the course of coculture. Supplementation of Tregs effectively abrogated hepatocyte-induced alloresponses and was primarily cell contact dependent. In conclusion, human hepatocytes induce a CD4(+) T cell alloresponse in vitro, which is associated with MHC class II up-regulation on hepatocytes and is susceptible to suppression by Tregs. Liver Transplantation 24 407-419 2018 AASLD.

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《Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society》 |2018年第3期|共13页
作者
DeTemple Daphne E.; Oldhafer Felix; Falk Christine S.; Chen-Wacker Chen; Figueiredo Constanca; Kleine Moritz; Ramackers Wolf; Timrott Kai; Lehner Frank; Klempnauer Juergen; Bock Michael; Vondran Florian W. R.;
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作者单位

Hannover Med Sch Dept Gen Visceral &

Transplant Surg Regenerat Med &

Expt Surg Carl Neuberg Str 1 D-30625 Hannover Germany;

Hannover Med Sch Dept Gen Visceral &

Transplant Surg Regenerat Med &

Expt Surg Carl Neuberg Str 1 D-30625 Hannover Germany;

Hannover Med Sch Inst Transplant Immunol Integrated Res &

Treatment Ctr Transplantat Hannover Germany;

Hannover Med Sch Inst Transfus Med Hannover Germany;

Hannover Med Sch Inst Transfus Med Hannover Germany;

Hannover Med Sch Dept Gen Visceral &

Transplant Surg Regenerat Med &

Expt Surg Carl Neuberg Str 1 D-30625 Hannover Germany;

Hannover Med Sch Dept Gen Visceral &

Transplant Surg Regenerat Med &

Expt Surg Carl Neuberg Str 1 D-30625 Hannover Germany;

Hannover Med Sch Dept Gen Visceral &

Transplant Surg Regenerat Med &

Expt Surg Carl Neuberg Str 1 D-30625 Hannover Germany;

Hannover Med Sch Dept Gen Visceral &

Transplant Surg Regenerat Med &

Expt Surg Carl Neuberg Str 1 D-30625 Hannover Germany;

Hannover Med Sch Dept Gen Visceral &

Transplant Surg Regenerat Med &

Expt Surg Carl Neuberg Str 1 D-30625 Hannover Germany;

Hannover Med Sch Dept Gastroenterol Hepatol &

Endocrinol Hannover Germany;

Hannover Med Sch Dept Gen Visceral &

Transplant Surg Regenerat Med &

Expt Surg Carl Neuberg Str 1 D-30625 Hannover Germany;

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正文语种 eng
中图分类肝及肝管;腹部外科学;
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2. Differential cell surface expression of rhesus macaque＇s major histocompatibility complex class I alleles Mamu-B＊1703 and Mamu-B＊0101 [J] . Dongyun Ouyang, Xianhui He, Lihui XU, 生物化学与生物物理学报：英文版 . 2010,第004期
3. Prokaryotic Expression and Monoclonal Antibody Preparation of Chicken Major Histocompatibility Complex Class II Molecules [J] . YE Ping, YU Wei-yi 动物与饲料科学：英文版 . 2010,第006期
4. Regulatory CD4(+) T Cells Recognize Major Histocompatibility Complex Class II Molecule-Restricted Peptide Epitopes of Apolipoprotein B [J] . Kimura Takayuki, Kobiyama Kouji, Winkels Holger, Circulation: An Official Journal of the American Heart Association . 2018,第11期

机译：调节CD4（+）T细胞识别脂蛋白B的主要组织相容性复合体II类分子限制肽表位
5. Self major histocompatibility complex class-II-specific regulatory CD4 T cells prevent both Th1- and Th2-mediated autoimmune diseases in the rat [J] . Lucette Pelletier, Magali Savignac, Emmanuel Xystrakis, Microbes and infection . 2001,第11期

机译：自身主要的组织相容性复合物II类特异性调节性CD4 T细胞可预防大鼠Th1和Th2介导的自身免疫性疾病
6. Interleukin-27 upregulates major histocompatibility complex class II expression in primary human endothelial cells through induction of major histocompatibility complex class II transactivator. [J] . Feng XM, Chen XL, Liu N, Human Immunology: Official Journal of the American Society for Histocompatibility and Immunogenetics . 2007,第12期

机译：白细胞介素27通过诱导主要组织相容性复合物II类反式激活因子来上调人类原代内皮细胞中主要组织相容性复合物II类的表达。
7. Invariant chain regulates the major histocompatibility complex class II peptide repertoire of cell-based cancer vaccines. [C] . Olesya Y. Chornoguz, Lydia Grmai, Alexei Gapeev, American Society for Mass Spectrometry Conference on Mass Spectrometry and Allied Topics . 2010

机译：不变链调节细胞基癌症疫苗的主要组织相容性复合体II类肽曲目。
8. Major histocompatibility complex class II-transfected tumor cells present peptides from endogenously encoded antigen in vitro and in vivo. [D] . Armstrong, Todd Donald. 1998

机译：主要的组织相容性复合物II类转染的肿瘤细胞在体内和体外呈现来自内源编码抗原的肽。
9. Hepatocyte‐induced CD4+ T cell alloresponse is associated with major histocompatibility complex class II up‐regulation on hepatocytes and suppressible by regulatory T cells [O] . Daphne E. DeTemple, Felix Oldhafer, Christine S. Falk, -1

机译：肝细胞诱导的CD4 + T细胞过敏反应与肝细胞上主要的组织相容性复合物II类上调相关并且可被调节性T细胞抑制
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11. Role of the Major Histocompatibility Complex in T Cell Activation of B Cell Subpopulations, Lyb-5(+) and Lyb-5(-) B Cell Subpopulations Differ in Their Requirement for Major Histocompatibility Complex-Restricted T Cell Recognition [R] . Singer, A., Morrissey, P. J., Hathcock, K. S., 1981

机译：主要组织相容性复合物在B细胞亚群，Lyb-5（+）和Lyb-5（ - ）B细胞亚群的T细胞活化中的作用不同于它们对主要组织相容性复杂限制性T细胞识别的要求

Hepatocyte-induced CD4(+) T cell alloresponse is associated with major histocompatibility complex class II up-regulation on hepatocytes and suppressible by regulatory T cells

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