Reversible activation of c-Myc in thymocytes enhances positive selection and induces proliferation and apoptosis in vitro.

In order to study the effect of c-Myc activation in T lymphocytes in vivo, we generated transgenic mice that express a 4-hydroxytamoxifen (4-OHT)-dependent switchable c-myc oncoprotein under the control of the proximal lck promoter. Activation of c-MycER causes no obvious alteration in T cell ontogeny. However, using MHC class I restricted H-Y-TCR transgenic mice, we found that c-Myc activation in vivo enhances the efficiency of positive selection. Moreover, splenic T cells derived from lck-c-mycER transgenic mice in which c-Myc had been activated exhibited increased proliferation in vitro in response to activation with anti-CD3/CD28 antibody. Activation of c-MycER also promotes apoptosis in thymocytes in vitro.