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  • Title: CTLA-4 overexpression inhibits T cell responses through a CD28-B7-dependent mechanism.
    Author: Engelhardt JJ, Sullivan TJ, Allison JP.
    Journal: J Immunol; 2006 Jul 15; 177(2):1052-61. PubMed ID: 16818761.
    Abstract:
    CTLA-4 has been shown to be an important negative regulator of T cell activation. To better understand its inhibitory action, we constructed CTLA-4 transgenic mice that display constitutive cell surface expression of CTLA-4 on CD4 and CD8 T cells. In both in vivo and in vitro T cell responses, CTLA-4 overexpression inhibits T cell activation. This inhibition is dependent on B7 and CD28, suggesting that overexpressed CTLA-4 inhibits responses by competing with CD28 for B7 binding or by interfering with CD28 signaling. In addition, expression of the transgene decreases the number of CD25+Foxp3+ T cells in these mice, but does not affect their suppressive ability. Our data confirm the activity of CTLA-4 as a negative regulator of T cell activation and that its action may be by multiple mechanisms.
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