TY - JOUR
T1 - CTLA-4 overexpression inhibits T cell responses through a CD28-B7-dependent mechanism
AU - Engelhardt, John J.
AU - Sullivan, Timothy J.
AU - Allison, James P.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2006/7/15
Y1 - 2006/7/15
N2 - 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 CB28, 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+Foxp 3+ 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.
AB - 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 CB28, 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+Foxp 3+ 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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U2 - 10.4049/jimmunol.177.2.1052
DO - 10.4049/jimmunol.177.2.1052
M3 - Article
C2 - 16818761
AN - SCOPUS:33745860066
SN - 0022-1767
VL - 177
SP - 1052
EP - 1061
JO - Journal of Immunology
JF - Journal of Immunology
IS - 2
ER -