| 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 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. Copyright © 2006 by The American Association of Immunologists, Inc. |
| Keywords: |
signal transduction; controlled study; protein expression; nonhuman; lymph nodes; cd8 antigen; cd8+ t lymphocyte; animal cell; mouse; animals; mice; mice, knockout; cells, cultured; culture medium; animal experiment; protein binding; down-regulation; cell differentiation; mice, inbred c57bl; transgenic mouse; mice, transgenic; lymphocyte activation; cell culture; cd4+ t lymphocyte; transgene; t-lymphocyte subsets; cd4 antigen; antigens, cd; mice, inbred cba; cytotoxic t lymphocyte antigen 4; antigen binding; epitopes, t-lymphocyte; t lymphocyte activation; cd28 antigen; antigens, cd28; b7 antigen; antigens, differentiation; g0 phase; cell surface; cho cell; antigens, cd80; binding, competitive; encephalomyelitis, autoimmune, experimental
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