CTLA-4 regulates induction of anergy in vivo

Immunity. 2001 Feb;14(2):145-55. doi: 10.1016/s1074-7613(01)00097-8.


The requirement for CTLA-4 during the induction of peripheral T cell tolerance in vivo was investigated using naive TCR transgenic T cells lacking CTLA-4. CTLA-4(-/-) T cells are resistant to tolerance induction, as demonstrated by their proliferative responses, IL-2 production, and progression into the cell cycle. Following exposure to a tolerogenic stimulus in vivo and restimulation in vitro, wild-type T cells are blocked at the late G1 to S restriction point of the cell cycle. In contrast, CTLA-4(-/-) T cells enter into the S phase of the cell cycle, as shown by downregulation of p27(kip1), elevated cdk2 kinase activity, and Rb hyperphosphorylation. Thus, CTLA-4 has an essential role in determining the outcome of T cell encounter with a tolerogenic stimulus.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abatacept
  • Animals
  • Antigens, CD
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / immunology*
  • Apoptosis
  • CTLA-4 Antigen
  • Cell Cycle
  • Clonal Anergy / immunology*
  • Cytokines / biosynthesis
  • DNA-Binding Proteins
  • Immune Tolerance
  • Immunoconjugates*
  • In Vitro Techniques
  • Interleukin-2 / biosynthesis
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Mice, Transgenic
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism


  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • Ctla4 protein, mouse
  • Cytokines
  • DNA-Binding Proteins
  • Immunoconjugates
  • Interleukin-2
  • Rag2 protein, mouse
  • V(D)J recombination activating protein 2
  • Abatacept