A role for CTLA-4-mediated inhibitory signals in peripheral T cell tolerance?

Novartis Found Symp. 1998;215:92-8; discussion 98-102, 186-90. doi: 10.1002/9780470515525.ch7.


Occupancy of the antigen receptor is not sufficient for activation of naïve T cells--additional co-stimulatory signals are required that can be provided only by 'professional' antigen-presenting cells. This two-signal model for T cell activation has been thought to provide a mechanism for the induction and maintenance of peripheral tolerance. Work over the past six years has demonstrated that the relevant co-stimulatory receptor on T cells is the molecule CD28. Recent data shows that the CD28 homologue CTLA-4 plays a role in negative regulation of T cell responses. Here we suggest that CTLA-4 may also serve as an attenuator of T cell-activating signals, raising the threshold of stimulation required to obtain full activation. The inhibitory signals mediated by CTLA-4 may provide an additional mechanism for the maintenance of peripheral tolerance.

Publication types

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

MeSH terms

  • Abatacept
  • Antigens, CD
  • Antigens, Differentiation / metabolism*
  • CD28 Antigens / metabolism
  • CTLA-4 Antigen
  • Immune Tolerance*
  • Immunoconjugates*
  • Immunosuppressive Agents / metabolism*
  • Signal Transduction
  • T-Lymphocytes / immunology*


  • Antigens, CD
  • Antigens, Differentiation
  • CD28 Antigens
  • CTLA-4 Antigen
  • Immunoconjugates
  • Immunosuppressive Agents
  • Abatacept