%0 Journal Article %J Eur J Immunol %D 2002 %T CTLA-4 regulates cell cycle progression during a primary immune response. %A Greenwald, Rebecca J %A Oosterwegel, Mariette A %A van der Woude, Diane %A Kubal, Anup %A Mandelbrot, Didier A %A Boussiotis, Vassiliki A %A Sharpe, Arlene H %K Animals %K Antigens, CD %K Antigens, CD80 %K Antigens, CD86 %K Antigens, Differentiation %K Cell Cycle %K Cell Cycle Proteins %K CTLA-4 Antigen %K Cyclin-Dependent Kinase Inhibitor p27 %K Cyclin-Dependent Kinases %K Cyclins %K Female %K G1 Phase %K Immunoconjugates %K In Vitro Techniques %K Interleukin-2 %K Lymphocyte Activation %K Membrane Glycoproteins %K Mice %K Mice, Knockout %K S Phase %K T-Lymphocytes %K Tumor Suppressor Proteins %X 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. %B Eur J Immunol %V 32 %P 366-73 %8 2002 Feb %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/11807776?dopt=Abstract %R 10.1002/1521-4141(200202)32:2<366::AID-IMMU366>3.0.CO;2-5