T cell anergy and costimulation

Immunol Rev. 2003 Apr;192:161-80. doi: 10.1034/j.1600-065x.2003.00009.x.


T lymphocytes play a key role in immunity by distinguishing self from nonself peptide antigens and regulating both the cellular and humoral arms of the immune system. Acquired, antigen-specific unresponsiveness is an important mechanism by which T cell responses to antigen are regulated in vivo. Clonal anergy is the term that describes T cell unresponsiveness at the cellular level. Anergic T cells do not proliferate or secrete interleukin (IL)-2 in response to appropriate antigenic stimulation. However, anergic T cells express the IL-2 receptor, and anergy can be broken by exogenous IL-2. Anergy can be induced by submitogenic exposure to peptide antigen in the absence of a costimulatory signal provided by soluble cytokines or by interactions between costimulatory receptors on T cells and counter-receptors on antigen-presenting cells. The molecular events that mediate the induction and maintenance of T cell anergy are the focus of this review. The molecular consequences of CD28-B7 interaction are discussed as a model for the costimulatory signal that leads to T cell activation rather than the induction of anergy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, CD
  • Antigens, Differentiation / metabolism
  • CD28 Antigens / chemistry
  • CD28 Antigens / metabolism
  • CTLA-4 Antigen
  • Cell Adhesion
  • Clonal Anergy*
  • GTP Phosphohydrolases / metabolism
  • Humans
  • Lymphocyte Activation
  • Mice
  • Molecular Sequence Data
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Structure, Tertiary
  • Receptors, Antigen, T-Cell / immunology
  • T-Lymphocytes / enzymology
  • T-Lymphocytes / immunology*


  • Antigens, CD
  • Antigens, Differentiation
  • CD28 Antigens
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Ctla4 protein, mouse
  • Receptors, Antigen, T-Cell
  • Phosphatidylinositol 3-Kinases
  • GTP Phosphohydrolases