CD152 (CTLA-4) regulates effector functions of CD8+ T lymphocytes by repressing Eomesodermin

Eur J Immunol. 2009 Mar;39(3):883-93. doi: 10.1002/eji.200838770.


CD8(+) T lymphocytes are required for effective host defense against pathogens and also for mediating effector responses against uncontrolled proliferating self-tissues. In this study, we determine that individual CD8(+) T cells are tightly controlled in their effector functions by CD152 (CTLA-4). We demonstrate that signals induced by CD152 reduce the frequency of IFN-gamma and granzyme B expressing CD8(+) T cells independently of the transcription factors T-bet or cKrox by selectively inhibiting accumulation of Eomesodermin mRNA and protein. Ectopic expression of Eomesodermin reversed the CD152-mediated inhibition of effector molecule production. Additionally, enhanced cytotoxicity of individual CD8(+) T cells differentiated in the absence of CD152 signaling was determined in vivo. These novel insights extend our understanding of how immune responses of CD8(+) T cells are selectively modulated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CTLA-4 Antigen
  • Cell Differentiation / immunology
  • Cytotoxicity, Immunologic / immunology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Gene Expression Regulation*
  • Granzymes / immunology
  • Granzymes / metabolism
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Ovalbumin / immunology
  • Signal Transduction / immunology
  • T-Box Domain Proteins / genetics*


  • Antigens, CD
  • CTLA-4 Antigen
  • Ctla4 protein, mouse
  • Eomes protein, mouse
  • T-Box Domain Proteins
  • Interferon-gamma
  • Ovalbumin
  • Granzymes