@article {542196,
	title = {Overexpression of the Ctla-4 isoform lacking exons 2 and 3 causes autoimmunity.},
	journal = {J Immunol},
	volume = {188},
	number = {1},
	year = {2012},
	month = {2012 Jan 1},
	pages = {155-62},
	abstract = {CTLA-4 is a potent inhibitor of T cell activation, primarily upon binding to its costimulatory ligands (B7.1 and B7.2) expressed on APCs. However, variants of CTLA-4 can also function independently of B7 molecules. 1/4CTLA-4 is a highly conserved isoform encoded by exons 1 and 4 of the Ctla4 gene that lacks the ligand-binding and the transmembrane domains, and as yet, its function is not known. To investigate the function of 1/4CTLA-4, we generated transgenic (Tg) mice overexpressing this variant. Cytokine production by 1/4CTLA-4 Tg T cells was elevated compared with wild type T cells. The frequency of CD44(high) memory T cells in 1/4CTLA-4 Tg mice was increased, and as the mice aged, the frequency further increased. 1/4CTLA-4 Tg mice >1 y old had increased expression of T cell activation markers and developed spontaneous autoimmunity, including elevated production of autoantibodies. In contrast with young 1/4CTLA-4 Tg mice, aged 1/4CTLA-4 Tg mice had elevated frequencies of Foxp3(+) regulatory T cells, but the regulatory T cells from these mice were not able to inhibit colitis development. Collectively, these data suggest that the function of the 1/4CTLA-4 isoform is distinct from that of CTLA-4 in that it enhances T cell activation and promotes autoimmunity rather than inhibiting immune responses.},
	keywords = {Animals, Autoantibodies, Autoimmune Diseases, Autoimmunity, Colitis, CTLA-4 Antigen, Exons, Immunologic Memory, Lymphocyte Activation, Mice, Mice, Transgenic, Protein Isoforms, T-Lymphocytes, Regulatory},
	issn = {1550-6606},
	doi = {10.4049/jimmunol.1102042},
	author = {Liu, Sue M and Sutherland, Andrew P R and Zhang, Zheng and Rainbow, Daniel B and Quintana, Francisco J and Paterson, Alison M and Sharpe, Arlene H and Oukka, Mohamed and Wicker, Linda S and Kuchroo, Vijay K}
}
