CTLA-4-mediated inhibition in regulation of T cell responses: Mechanisms and manipulation in tumor immunotherapy

C. A. Chambers, M. S. Kuhns, J. G. Egen, J. P. Allison

Research output: Contribution to journalReview articlepeer-review

862 Scopus citations


The T cell compartment of adaptive immunity provides vertebrates with the potential to survey for and respond specifically to an incredible diversity of antigens. The T cell repertoire must be carefully regulated to prevent unwanted responses to self. In the periphery, one important level of regulation is the action of costimulatory signals in concert with T cell antigen-receptor (TCR) signals to promote full T cell activation. The past few years have revealed that costimulation is quite complex, involving an integration of activating signals and inhibitory signals from CD28 and CTLA-4 molecules, respectively, with TCR signals to determine the outcome of a T cell's encounter with antigen. Newly emerging data suggest that inhibitory signals mediated by CTLA-4 not only can determine whether T cells become activated, but also can play a role in regulating the clonal representation in a polyclonal response. This review primarily focuses on the cellular and molecular mechanisms of regulation by CTLA-4 and its manipulation as a strategy for tumor immunotherapy.

Original languageEnglish (US)
Pages (from-to)565-594
Number of pages30
JournalAnnual review of immunology
StatePublished - 2001


  • CD28
  • Costimulation
  • Cytotoxic T lymphocyte antigen-4 (CTLA-4)
  • T cell activation
  • T cell regulation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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