DEVELOPMENTAL AND FUNCTIONAL IMPAIRMENT OF T-CELLS IN MICE LACKING CD3-ZETA CHAINS

CD3zeta is a component of the T cell antigen receptor (TCR) complex an d is important for signal transduction. We have established mice selec tively lacking CD3zeta but able to express CD3eta, a polypeptide produ ced from the same locus through alternative splicing, using the method of gene targeting in embryonic stem cells. In homozygous mutant mice, the numbers of thymocytes and peripheral T cells were greatly reduced and the expression levels of TCR on these cells were 5-fold lower tha n those on wild-type cells. By contrast, TCRgammadelta+ intestinal int raepithelial lymphocytes were not obviously affected by the mutation. T cells from homozygous mutants exhibited an impaired proliferative re sponse. These results imply that CD3zeta has a critical role in the de velopment and signal transduction of T cells in vivo.