T cells in the control of organ-specific autoimmunity.

نویسندگان

  • Jeffrey A Bluestone
  • Hélène Bour-Jordan
  • Mickie Cheng
  • Mark Anderson
چکیده

Immune tolerance is critical to the avoidance of unwarranted immune responses against self antigens. Multiple, non-redundant checkpoints are in place to prevent such potentially deleterious autoimmune responses while preserving immunity integral to the fight against foreign pathogens. Nevertheless, a large and growing segment of the population is developing autoimmune diseases. Deciphering cellular and molecular pathways of immune tolerance is an important goal, with the expectation that understanding these pathways will lead to new clinical advances in the treatment of these devastating diseases. The vast majority of autoimmune diseases develop as a consequence of complex mechanisms that depend on genetic, epigenetic, molecular, cellular, and environmental elements and result in alterations in many different checkpoints of tolerance and ultimately in the breakdown of immune tolerance. The manifestations of this breakdown are harmful inflammatory responses in peripheral tissues driven by innate immunity and self antigen-specific pathogenic T and B cells. T cells play a central role in the regulation and initiation of these responses. In this Review we summarize our current understanding of the mechanisms involved in these fundamental checkpoints, the pathways that are defective in autoimmune diseases, and the therapeutic strategies being developed with the goal of restoring immune tolerance.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

CTLA4 Gene Variants in Autoimmunity and Cancer: a Comparative Review

Gene association studies are less appealing in cancer compared to autoimmune diseases. Complexity, heterogeneity, variation in histological types, age at onset, short survival, and acute versus chronic conditions are cancer related factors which are different from an organ specific autoimmune disease, such as Grave’s disease, on which a large body of multicentre data is accumulated. For years t...

متن کامل

An In Vitro Assay to Evaluate the Immunomodulatory Effects of Unrestricted Somatic Stem Cells

Background: Unrestricted somatic stem cells (USSC) are cord blood stem cells that have been considered as candidates for the regulation of immune responses. Therefore, potential exists for their use in the suppression of immune response after transplantation surgery. Objective: The aim of this study was evaluation of the effect of USSC on mixed lymphocyte reaction (MLR) as a model for graft rej...

متن کامل

Protection against autoimmunity in nonlymphopenic hosts by CD4+ CD25+ regulatory T cells is antigen-specific and requires IL-10 and TGF-beta.

CD4+ CD25+ regulatory T cells (T(Reg)) play a critical role in the control of autoimmunity. However, little is known about how T(Reg) suppress self-reactive T cells in vivo, thus limiting the development of T(Reg)-based therapy for treating autoimmune diseases. This is in large part due to the dependency on a state of lymphopenia to demonstrate T(Reg)-mediated suppression in vivo and the unknow...

متن کامل

Human Leukocyte Antigen-G Expression on Dendritic Cells Induced by Transforming Growth Factor-β1 and CD4+ T Cells Proliferation

Background: During antigen capture and processing, mature dendritic cells (DC) express large amounts of peptide-MHC complexes and accessory molecules on their surface. DC are antigen-presenting cells that have an important role in tolerance and autoimmunity. The transforming growth factor-beta1 (TGF-β1) cytokine has a regulatory role on the immune and non-immune cells. The aim of this study is ...

متن کامل

Protection against Autoimmunity in Nonlymphopenic Hosts by CD 4 CD 25 Regulatory T Cells Is Antigen - Specific and Requires IL - 10 and TGF - 1

CD4 CD25 regulatory T cells (TReg) play a critical role in the control of autoimmunity. However, little is known about how TReg suppress self-reactive T cells in vivo, thus limiting the development of TReg-based therapy for treating autoimmune diseases. This is in large part due to the dependency on a state of lymphopenia to demonstrate TReg-mediated suppression in vivo and the unknown Ag speci...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • The Journal of clinical investigation

دوره 125 6  شماره 

صفحات  -

تاریخ انتشار 2015