@article {542806,
	title = {Mouse inducible costimulatory molecule (ICOS) expression is enhanced by CD28 costimulation and regulates differentiation of CD4+ T cells.},
	journal = {J Immunol},
	volume = {165},
	number = {9},
	year = {2000},
	month = {2000 Nov 1},
	pages = {5035-40},
	abstract = {The inducible costimulatory (ICOS) molecule is expressed by activated T cells and has homology to CD28 and CD152. ICOS binds B7h, a molecule expressed by APC with homology to CD80 and CD86. To investigate regulation of ICOS expression and its role in Th responses we developed anti-mouse ICOS mAbs and ICOS-Ig fusion protein. Little ICOS is expressed by freshly isolated mouse T cells, but ICOS is rapidly up-regulated on most CD4(+) and CD8(+) T cells following stimulation of the TCR. Strikingly, ICOS up-regulation is significantly reduced in the absence of CD80 and CD86 and can be restored by CD28 stimulation, suggesting that CD28-CD80/CD86 interactions may optimize ICOS expression. Interestingly, TCR-transgenic T cells differentiated into Th2 expressed significantly more ICOS than cells differentiated into Th1. We used two methods to investigate the role of ICOS in activation of CD4(+) T cells. First, CD4(+) cells were stimulated with beads coated with anti-CD3 and either B7h-Ig fusion protein or control Ig fusion protein. ICOS stimulation enhanced proliferation of CD4(+) cells and production of IFN-gamma, IL-4, and IL-10, but not IL-2. Second, TCR-transgenic CD4(+) T cells were stimulated with peptide and APC in the presence of ICOS-Ig or control Ig. When the ICOS:B7h interaction was blocked by ICOS-Ig, CD4(+) T cells produced more IFN-gamma and less IL-4 and IL-10 than CD4(+) cells differentiated with control Ig. These results demonstrate that ICOS stimulation is important in T cell activation and that ICOS may have a particularly important role in development of Th2 cells.},
	keywords = {Adjuvants, Immunologic, Animals, Antigens, CD28, Antigens, Differentiation, T-Lymphocyte, Binding, Competitive, CD4-Positive T-Lymphocytes, Cell Differentiation, Cytokines, Immunoglobulins, Inducible T-Cell Co-Stimulator Ligand, Inducible T-Cell Co-Stimulator Protein, Ligands, Lymphocyte Activation, Mice, Mice, Inbred BALB C, Mice, Knockout, Mice, Transgenic, Proteins, Recombinant Fusion Proteins, Th1 Cells, Th2 Cells, Up-Regulation},
	issn = {0022-1767},
	author = {McAdam, A J and Chang, T T and Lumelsky, A E and Greenfield, E A and Boussiotis, V. A. and Duke-Cohan, J S and Chernova, T and Malenkovich, N and Jabs, C and Kuchroo, V K and Ling, V and Collins, M and Sharpe, A. H. and Freeman, G. J.}
}
