CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells

J Exp Med. 1996 Jun 1;183(6):2533-40. doi: 10.1084/jem.183.6.2533.


While interactions between CD28 and members of the B7 family costimulate and enhance T cell responses, recent evidence indicates that the CD28 homologue CTLA-4 plays a downregulatory role. The mechanism by which this occurs is not clear, but it has been suggested that CTLA-4 terminates ongoing responses of activated T cells, perhaps by induction of apoptosis. Here we demonstrate that CTLA-4 engagement by antibody cross-linking or binding to B7 inhibits proliferation and accumulation of the primary T cell growth factor, IL-2, by cells stimulated with anti-CD3 and anti-CD28. This inhibition is not a result of enhanced cell death. Rather it appears to result from restriction of transition from the G1 to the S phase of the cell cycle. Our observation that upregulation of both the IL-2R alpha chain and the CD69 activation antigen are inhibited by CTLA-4 engagement supplies further evidence that CTLA-4 restricts the progression of T cells to an activated state. Together this data demonstrates that CTLA-4 can regulate T cell activation in the absence of induction of apoptotic cell death.

Publication types

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

MeSH terms

  • Abatacept
  • Animals
  • Antibodies
  • Antigens, CD
  • Antigens, Differentiation / immunology
  • Antigens, Differentiation / physiology*
  • Apoptosis
  • CD28 Antigens / immunology
  • CD3 Complex / immunology
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CTLA-4 Antigen
  • Cell Cycle / immunology*
  • Cells, Cultured
  • Cells, Immobilized
  • Cross-Linking Reagents
  • Immunoconjugates*
  • Interleukin-2 / biosynthesis*
  • Kinetics
  • Latex
  • Lymph Nodes / immunology
  • Lymphocyte Activation*
  • Mice
  • Mice, Inbred BALB C
  • Microspheres
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology*
  • Time Factors


  • Antibodies
  • Antigens, CD
  • Antigens, Differentiation
  • CD28 Antigens
  • CD3 Complex
  • CTLA-4 Antigen
  • Cross-Linking Reagents
  • Ctla4 protein, mouse
  • Immunoconjugates
  • Interleukin-2
  • Latex
  • Abatacept