CTLA-4: From mechanism to autoimmune therapy

Int Immunopharmacol. 2020 Mar:80:106221. doi: 10.1016/j.intimp.2020.106221. Epub 2020 Jan 30.

Abstract

CD28 and CTLA-4 are both important stimulatory receptors for the regulation of T cell activation. Because receptors share common ligands, B7.1 and B7.2, the expression and biological function of CTLA-4 is important for the negative regulation of T cell responses. Therefore, elimination of CTLA-4 can result in the breakdown of immune tolerance and the development of several diseases such as autoimmunity. Inhibitory signals of CTLA-4 suppress T cell responses and protect against autoimmune diseases in many ways. In this review, we summarize the structure, expression and signaling pathway of CTLA-4. We also highlight how CTLA-4 defends against potentially self-reactive T cells. Finally, we discuss how the CTLA-4 regulates a number of autoimmune diseases that indicate manipulation of this inhibitory molecule is a promise as a strategy for the immunotherapy of autoimmune diseases.

Publication types

  • Review

MeSH terms

  • Abatacept / pharmacology
  • Abatacept / therapeutic use
  • Animals
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / pathology
  • Autoimmunity / drug effects
  • Autoimmunity / genetics
  • CTLA-4 Antigen / agonists
  • CTLA-4 Antigen / genetics
  • CTLA-4 Antigen / immunology
  • CTLA-4 Antigen / metabolism*
  • Clinical Trials as Topic
  • Disease Models, Animal
  • Humans
  • Immune Tolerance / drug effects
  • Immune Tolerance / genetics
  • Immunoconjugates / pharmacology
  • Immunoconjugates / therapeutic use
  • Immunosuppressive Agents / pharmacology*
  • Immunosuppressive Agents / therapeutic use
  • Lymphocyte Activation / drug effects
  • Signal Transduction / drug effects*
  • Signal Transduction / immunology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Treatment Outcome

Substances

  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Ctla4 protein, mouse
  • Immunoconjugates
  • Immunosuppressive Agents
  • Abatacept