新功能、新界面、新体验,扫描即可下载生物谷APP!
首页 » 免疫学 » Nat.Rev.Immuno:树突状细胞和移植免疫耐受的研究综述

Nat.Rev.Immuno:树突状细胞和移植免疫耐受的研究综述

来源:生物谷 2007-07-26 09:36

生物谷报道:近年来,人们对于树突状细胞的概念从单一的作为免疫反应的激活者,转换到它们是免疫调节的关键细胞,其中包括它们能够诱导并维持免疫耐受。研究人员进一步的认识到树突状细胞在表型和功能上的可塑性,发展了离体和在体地调控它们的生长与成熟的技术,并以此为基础利用它们内在的致耐受性来发挥治疗作用。

发表在最新一期《自然免疫学综述》上的一篇文章,系统地讨论了树突状细胞在移植免疫耐受中的作用。在这篇综述中,研究人员整合了各种有用的关于树突状细胞在移植中诱导免疫耐受作用的资料。

 

 

FIGURE 1 | Roles of CD8- (myeloid) and CD8 + DCs of mouse secondary lymphoid organs in T-cell immunity and peripheral tolerance.

The diagram incorporates observations from numerous studies, mainly on splenic dendritic cells (DCs) in mice, which are the most complete source of information on natural DCs in vivo. After exposure to danger signals and/or activation and maturation stimuli, immature splenic CD8- DCs of the red pulp and marginal zone mobilize to the T-cell areas of the spleen and, like the CD8 + DCs that reside constitutively in the T-cell areas, increase the surface expression of MHC and co-stimulatory molecules (CD80/CD86), the secretion of interleukin-12p70 (IL-12p70) and enhance their ability to stimulate naive or memory T cells. The interaction between CD154 (also known as CD40L), which is expressed transiently by activated T cells, and CD40 on the DC surface induces further activation and maturation of both DC subsets. CD8- mature DCs might induce the expansion of regulatory T cells as an inhibitory loop to restrain the T-cell response and/or as a mechanism to prevent the breach of peripheral tolerance against those self antigens presented simultaneously with the foreign antigen by the same mature DC. By contrast, in the steady state (tolerance), CD8- and CD8 + DCs remain quiescent after capturing and processing exogenous antigen (throughthe internalization of apoptotic cells, vesicles and/or soluble molecules — the last of which has been shown elegantly in experimental models by fusing the antigen to antibodies that specifically target different subsets of DCs in vivo101, 102. These quiescent (semi-mature) DCs express low levels of co-stimulatory molecules and therefore induce deficient activation of naive T cells, and induce T-cell apoptosis or anergy and probably the generation and/or expansion of regulatory T cells. The interaction of surface CD80/CD86 on both splenic DC subsets with cytotoxic T-lymphocyte antigen 4 (CTLA4; which can be soluble in the form of the CTLA4–immunoglobulin fusion protein (not shown) or membrane-bound on regulatory T cells) enhances the synthesis of functional indoleamine 2,3-dioxygenase (IDO). IDO is an enzyme that catalyzes the depletion of the essential amino acid tryptophan, resulting in the inhibition of T-cell proliferation, and produces tryptophan-derived metabolites that promote T-cell apoptosis. IDO synthesis by CD8 + DCs requires autocrine release of interferon- (IFN ) and is inhibited by autocrine secretion of IL-6, a cytokine that downregulates expression of the IFN -receptor (IFNGR) chain CD119. Splenic CD8 + DCs express the functional CD95 ligand (CD95L), which can trigger T-cell death.

 

 

原文出处:

Nature Review Immunology  August 2007 Vol 7 No 8

Tolerogenic dendritic cells and the quest for transplant tolerance

Adrian E. Morelli & Angus W. Thomson

p610 | doi:10.1038/nri2132

Tolerogenic dendritic cells (DCs) have potential as therapeutic tools for preventing transplant rejection. This Review describes what constitutes a tolerogenic DC, how tolerogenic DCs can be induced, the mechanisms by which they mediate tolerance and the future challenges facing DC-based immunotherapy.

·                             Abstract

·                             Full Text

·                             PDF (905 KB)

·                             Supplementary information

 

 

作者简介:

Angus W. Thomson , Ph.D., D.Sc.
Professor


Department of Immunology

Research Interests

  • Understanding the role of dendritic cells in liver transplant tolerance. Here we seek to elucidate the role of dendritic leukocytes, - highly specialized antigen-presenting cells, in determining the balance between organ transplantation tolerance and immunity. Studies involve elucidation of the roles of key signaling molecules in the dialogue between dendritic cells (DC) and T cells, and investigation of the function of DC in organ allograft models.
  • Genetic engineering of dendritic cells for transplantation tolerance. Using different vector delivery systems (retroviral/adenoviral), engineering dendritic cells to express genes encoding immunosuppressive molecules, including viral interleukin-10, Fas Ligand, and CTLA4Ig. Adoptive transfer of these cells to allogeneic hosts and their interaction with host T lymphocytes may promote tolerance induction, while minimizing the undesirable systemic effects of the immunosuppressive molecules.
  • Monitoring tolerance in human transplant recipients. Selected techniques including dendritic subset analysis and quantification of allospecific T cell responses in vitro and in vivo are being applied with the aim of establishing assays that correlate with and are predicative of transplantation tolerance.

Education

  • B.Sc. (Hons) - University Aberdeen (1970)
  • M.Sc. - University Birmingham (Birmingham, UK - 1971)
  • Ph.D. - University Aberdeen (1974)
  • D.Sc. - University Aberdeen (1986)

Academic Affiliation

  • Professor of Surgery, Immunology and Molecular Genetics & Biochemistry, University of Pittsburgh School of Medicine
  • Director of Transplant Immunology, Thomas E. Starzl Transplantation Institute
  • Member, Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center
  • Member, University of Pittsburgh Cancer Institute

Publications

  • Hackstein H, and Thomson AW. (2004) Dendritic cells: emerging pharmacologic targets of immunosuppressive drugs. Nature Reviews Immunology. 4:24-34.
  • Morelli AE and Thomson AW (2003) Dendritic cells: regulators of alloimmunity and opportunities for tolerance induction. Immunological Reviews. 196:125-146.
  • Hackstein H, Taner T, Zahorchak AF, Morelli AE, Logar AJ and Thomson AW. (2003) Rapamycin inhibits IL-4-induced dendritic cell maturation in vivo and dendritic cell mobilization and function in vivo. Blood. 101:4457-63.
  • Morelli AE, Larregina A, Shufesky WJ, Zahorchak AF, Logar AJ, Papworth GD, Wang Z, Watkins SC, Falo LD and Thomson AW. (2003) Internalization of circulating apoptotic cells by splenic marginal zone dendritic cells: dependence on complement receptors and impact on cytokine production. Blood 101:611-20.
  • Mazariegos GV, Zahorchak AF, Reyes J, Ostrowski L, Zeevi A, and Thomson AW. (2003) Dendritic cell subset ratio in peripheral blood correlates with successful withdrawal of immunosuppression in liver transplant patients. Am J Transplantation 3:689-96.

Adrian Morelli

 

 

相关报道:

流式细胞仪检测外周血树突状细胞 

树突状细胞对单纯疱疹病毒的双重识别 

树突状细胞瘤苗新进展 

日科学家用抑制性树突状细胞治愈小鼠败血症

树突状细胞上与HIV传播有关的分子 

 

用阻断剂诱导肝细胞移植免疫耐受 

 

Nat.Immu免疫耐受和免疫排斥的新机制被发现 

Nature:促进免疫耐受的肥大细胞 

治疗性乙肝蛋白疫苗有望打破乙肝免疫耐受 

细胞凋亡和免疫耐受 

免疫耐受的机制

免疫耐受的维持和终止

温馨提示:87%用户都在生物谷APP上阅读,扫描立刻下载! 天天精彩!


相关标签

最新会议 培训班 期刊库