Normal thymic selection, normal viability and decreased lymphoproliferation in T cell receptor-transgenic CTLA-4-deficient mice

Eur J Immunol. 1997 Aug;27(8):1887-92. doi: 10.1002/eji.1830270811.


CTLA-4 is a T cell surface receptor essential for the negative regulation of T cell activation. In the CTLA-4-deficient mouse, a dramatic accumulation of activated peripheral T cells effects extensive damage to host tissues, resulting in mortality within 5 weeks of age. To determine whether the accumulation of activated T cells in CTLA-4(-/-) mice is due to a defect in thymic selection, we examined negative selection in CTLA-4(-/-) mice using two transgenic T cell receptor (TCR) models of thymic selection. Neither the H-Y-specific TCR nor the lymphocytic choriomeningitis virus (LCMV)-specific TCR transgenic models revealed a defect in positive or negative selection in CTLA-4(-/-) mice in vivo or in vitro. In fact, the negatively selecting phenotype of male H-YTCR-transgenic mice greatly mitigated the accumulation of activated peripheral T cells. Further, peripheral CTLA-4(-/-) T cells expressing a single LMCV-specific transgenic TCR did not have an activated phenotype, indicating that CTLA-4(-/-) T cells require specific antigen for proliferation. These results demonstrate that specific antigen is required for the lymphoproliferation observed in CTLA-4(-/-) mice, and that CTLA-4 deficiency does not lead to a gross defect in negative selection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abatacept
  • Animals
  • Antigens, CD
  • Antigens, Differentiation / metabolism*
  • Apoptosis / immunology
  • Base Sequence
  • CTLA-4 Antigen
  • Cell Survival / immunology
  • DNA Primers / genetics
  • Female
  • H-Y Antigen / metabolism
  • Immunoconjugates*
  • Lymphocyte Activation
  • Lymphocytic choriomeningitis virus / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Polymerase Chain Reaction
  • Receptors, Antigen, T-Cell / genetics*
  • Thymus Gland / cytology*
  • Thymus Gland / immunology*


  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • Ctla4 protein, mouse
  • DNA Primers
  • H-Y Antigen
  • Immunoconjugates
  • Receptors, Antigen, T-Cell
  • Abatacept