Duration of TCR stimulation determines costimulatory requirement of T cells

Immunity. 1996 Jul;5(1):41-52. doi: 10.1016/s1074-7613(00)80308-8.


Current models suggest that T cells that receive only signal-1 through antigenic stimulation of the T cell receptor (TCR) become anergic, but will mount an immune response when a costimulatory signal-2 is provided. Using mice deficient for an important costimulatory molecule, CD28, we show that a transient signal-1 alone, either through infection with an abortively replicating virus, or through injection of viral peptide, anergizes CD8+ T cells, demonstrating the biological relevance of T cell anergy in vivo. However, in the absence of CD28, continued presence of signal-1 alone, either through prolonged viral replication or repeated injection of peptide, prevents the induction of anergy and generates a functional T cell response in vivo.

MeSH terms

  • Animals
  • Antigens, Viral / administration & dosage
  • Antigens, Viral / immunology
  • CD28 Antigens / immunology
  • CD28 Antigens / metabolism
  • Clonal Deletion
  • Cytotoxicity, Immunologic*
  • Dose-Response Relationship, Immunologic
  • Immune Tolerance
  • Lymphocyte Activation*
  • Lymphocytic choriomeningitis virus / immunology
  • Lymphocytic choriomeningitis virus / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Mutant Strains
  • Receptors, Antigen, T-Cell / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Virus Replication / immunology


  • Antigens, Viral
  • CD28 Antigens
  • Receptors, Antigen, T-Cell