Soluble HLA-G Inhibits Cell Cycle Progression in Human Alloreactive T Lymphocytes

• Published in: Journal of Immunology Vol. 176; no. 3; pp. 1331 - 1339
• Main Authors: Bahri, Rajia, Hirsch, Francois, Josse, Adeline, Rouas-Freiss, Nathalie, Bidere, Nicolas, Vasquez, Aime, Carosella, Edgardo D, Charpentier, Bernard, Durrbach, Antoine
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.02.2006
• Subjects: Apoptosis - immunology; Cell Cycle - immunology; Cell Line, Tumor; Cell Proliferation; Cytokines - antagonists & inhibitors; Cytokines - biosynthesis; Growth Inhibitors - physiology; Histocompatibility Antigens Class I - physiology; HLA Antigens - physiology; HLA-G Antigens; Humans; Immunophenotyping; Lymphocyte Activation - immunology; Solubility; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.176.3.1331

HLA-G is involved in regulating T cell responses. Various mechanisms have been proposed to explain the inhibition of T cell proliferation. In this context, the possible role of HLA-G in cell cycle regulation remains to be explored. Using stably transfected M8 cells expressing the secreted isoform (HLA-G5) of HLA-G, we investigated the role of HLA-G in inducing apoptosis and in controlling the cell cycle of activated T cells. Soluble HLA-G (HLA-G5) inhibited both CD4 and CD8 T cell proliferation. However, HLA-G5 did not induce T cell apoptosis, as determined by 3,3'-diethyloxacarbocyanine and propidium iodine labeling. It induced accumulation of the retinoblastoma protein, but not its phosphorylated and active form. Treatment of activated T cells with HLA-G5 also reduced the amounts of cyclin D2, E, A, and B by >80%. In contrast, it induced an accumulation of p27kip, but not p21cip, in activated T cells. HLA-G does not induce apoptosis of alloreactive T cells, but induces p27kip1 and inhibits cell cycle progression.