@article {542741,
	title = {CTLA-4 regulates cell cycle progression during a primary immune response.},
	journal = {Eur J Immunol},
	volume = {32},
	number = {2},
	year = {2002},
	month = {2002 Feb},
	pages = {366-73},
	abstract = {Engagement of CTLA-4 is critical for inhibiting T cell immune responses. Recent studies have shown that CTLA-4 plays a key role in regulating peripheral T cell tolerance. It has been suggested that one mechanism by which CTLA-4 performs this function is by regulating cell cycle progression. Here, we investigate in depth the role of CTLA-4 in regulating cell cycle progression in naive T cells by comparing the immune responses in the absence or presence of CTLA-4. In the absence of CLTA-4, T cells exhibit marked increases in T cell proliferation, IL-2 mRNA and protein secretion, and cells cycling in the S and G2-M phase. Analyses of cyclins, cyclin-dependent kinases, and cell cycle inhibitors involved in the transition from the G1 to S phase reveal that cell cycle progression is prolonged in the absence of CTLA-4. This is due to the early exit from the G1 phase, entry into the S phase, and prolonged S phase period. Re-expression of the cell cycle inhibitor p27(kip1) is delayed in the absence of CTLA-4. These studies demonstrate that the B7 : CTLA-4 pathway exerts its major effects on T cell immune responses via regulation of the cell cycle.},
	keywords = {Animals, Antigens, CD, Antigens, CD80, Antigens, CD86, Antigens, Differentiation, Cell Cycle, Cell Cycle Proteins, CTLA-4 Antigen, Cyclin-Dependent Kinase Inhibitor p27, Cyclin-Dependent Kinases, Cyclins, Female, G1 Phase, Immunoconjugates, In Vitro Techniques, Interleukin-2, Lymphocyte Activation, Membrane Glycoproteins, Mice, Mice, Knockout, S Phase, T-Lymphocytes, Tumor Suppressor Proteins},
	issn = {0014-2980},
	doi = {10.1002/1521-4141(200202)32:2\&$\#$60;366::AID-IMMU366\&$\#$62;3.0.CO;2-5},
	author = {Greenwald, Rebecca J and Oosterwegel, Mariette A and van der Woude, Diane and Kubal, Anup and Mandelbrot, Didier A and Boussiotis, Vassiliki A and Sharpe, Arlene H}
}
