Yin-Yang of costimulation: crucial controls of immune tolerance and function

Immunol Rev. 2009 May;229(1):88-100. doi: 10.1111/j.1600-065X.2009.00769.x.


In addition to signals from the T-cell receptor complex, it has been recognized for many years that a 'second' signal, most notably from CD28, is also important in T-cell activation. In the recent years, many new members of CD28 family as well as the molecules that share structural homology to CD28 ligands CD80 and CD86 have been discovered. Interestingly, some of these proteins function to dampen T-cell activation and regulate the induction of T-cell tolerance. Therefore, positive and negative costimulation are the two sides of the coin to fine tune T-cell receptor signaling to determine the outcome of T-cell receptor engagement-tolerance versus function.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibody Formation / immunology
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte
  • Apoptosis Regulatory Proteins / immunology
  • Apoptosis Regulatory Proteins / metabolism
  • Autoimmunity / immunology
  • B7 Antigens
  • B7-1 Antigen / immunology
  • B7-1 Antigen / metabolism
  • CD28 Antigens / immunology*
  • CD28 Antigens / metabolism
  • Humans
  • Immune Tolerance*
  • Inducible T-Cell Co-Stimulator Protein
  • Lymphocyte Activation*
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / metabolism
  • Signal Transduction / immunology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism


  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • Apoptosis Regulatory Proteins
  • B7 Antigens
  • B7-1 Antigen
  • CD276 protein, human
  • CD28 Antigens
  • ICOS protein, human
  • Inducible T-Cell Co-Stimulator Protein
  • Receptors, Antigen, T-Cell
  • Receptors, Immunologic