CTLA-4: A key regulatory point in the control of autoimmune disease

Kenneth J. Scalapino, David I. Daikh

Research output: Contribution to journalReview articlepeer-review

137 Scopus citations

Abstract

Chronic autoimmune disease in humans is the result of a failure to control autoreactive immune cells in the periphery. This control is largely achieved by inhibition of newly activated and memory cells. A number of negative immune regulatory pathways have been characterized. The cell surface coreceptor cytotoxic T-lymphocyte antigen-4 (CTLA-4) has emerged as a critical attenuator of T-cell activation and an essential component of the regulatory systems that serve to maintain peripheral tolerance. CTLA-4 expression is induced on the surface of T cells after they have received a costimulatory signal from antigen-presenting cells (APCs) via engagement of CD28 on the T-cell surface. CTLA-4 attenuates this costimulation by competing for CD28 ligands and through direct effects on APCs via the same ligands utilized by CD28. A large number of genetic association studies suggest that the CTLA-4 gene is a locus of susceptibility to autoimmune disease. However, specific functional defects in the CTLA-4 gene in patients have not been identified to date. Elucidating the role of CTLA-4 in immune tolerance has also led to a number of therapeutic applications, particularly in the treatment of malignancy and autoimmune disease.

Original languageEnglish (US)
Pages (from-to)143-155
Number of pages13
JournalImmunological reviews
Volume223
Issue number1
DOIs
StatePublished - Jun 2008
Externally publishedYes

Keywords

  • Autoimmunity
  • Regulatory T cells
  • Suppression
  • Tcells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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