Role of ICOS versus CD28 in antiviral immunity

Eur J Immunol. 2002 Dec;32(12):3376-85. doi: 10.1002/1521-4141(200212)32:12<3376::AID-IMMU3376>3.0.CO;2-Y.


The costimulatory protein ICOS is inducibly expressed on activated T cells. Previous results have shown that ICOS(-/-) mice are defective in germinal center formation, antibody (Ab) production and class switch as well as Th1 and Th2 cytokine production in response to protein or parasite antigens. However, ICOS-Ig failed to block antiviral Ab responses. To date the immune response to viruses has not been examined in ICOS(-/-) mice. In this report we compared antiviral Ab responses to LCMV, VSV and influenza virus in ICOS(-/-) versus wild-type mice. Our results show that ICOS is important in the Ab response to all three viruses, with greater effects on primary as compared to secondary responses. Although ICOS(-/-) mice are impaired in some immune responses following influenza infection, the effects were less severe than for CD28(-/-) mice. There was no defect in initial influenza-specific CD8 T cell expansion in ICOS(-/-) mice or in cytotoxic effector function. However, ICOS was important in maintaining CD4 cytokine production and CD8 T cell numbers late in the primary response. Upon secondary infection, ICOS(-/-) mice show wild-type levels of influenza-specific CD8 T cells, whereas CD28(-/-) mice show greatly impaired secondary CD8 T cell expansion. Overall, our results show that ICOS plays a clear role in the primary response to viruses at the level of Ab production, germinal center formation and Th cytokine production, but has diminished effects following secondary viral challenge.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / biosynthesis
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • Antigens, Differentiation, T-Lymphocyte / metabolism*
  • CD28 Antigens / metabolism*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Female
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / classification
  • Immunoglobulin Switch Region
  • Inducible T-Cell Co-Stimulator Protein
  • Interleukin-2 / biosynthesis
  • Lymphocytic choriomeningitis virus / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Orthomyxoviridae / immunology
  • Orthomyxoviridae Infections / immunology
  • Vesicular stomatitis Indiana virus / immunology
  • Viruses / immunology*


  • Antibodies, Viral
  • Antigens, Differentiation, T-Lymphocyte
  • CD28 Antigens
  • Icos protein, mouse
  • Immunoglobulin G
  • Inducible T-Cell Co-Stimulator Protein
  • Interleukin-2