Accelerated proliferation and interleukin-2 production of thymocytes by stimulation of soluble anti-CD3 monoclonal antibody in transgenic mice carrying a rabbit protein kinase C alpha.

Protein kinase C (PKC) has been believed to play an important role in the differentiation/proliferation of various kinds of mammalian cells. To analyze its function in living animals, we have established a transgenic mouse line carrying rabbit protein kinase C alpha cDNA under the control of the regulatory element of human CD2. Thymocytes of these transgenic mice overexpressed PKC alpha. Interestingly, the increase of PKC alpha was detected mainly in membrane fractions of transgenic thymocytes. Although the transgenic thymocytes did not show any distinct proliferative features in vivo, they displayed a unique property to extensively proliferate and produce interleukin-2 (IL-2) in response to the stimulation by a soluble form of anti-CD3 monoclonal antibody (mAb), an incomplete agonist for proliferation of normal thymocytes. Furthermore, co-stimulation of the phorbol 12-myristate 13-acetate and anti-CD3 mAb intensely provoked the transgenic thymocytes to release IL-2. For the first time this result provided the direct evidence that PKC alpha translocated to the cell membrane of thymocytes works as an active second messenger of the T cell receptor-CD3 complex-delivered signal for proliferation and IL-2 production.