Essential and partially overlapping role of CD3 gamma and CD3 delta for development of alpha beta and gamma delta T lymphocytes

CD3 gamma and CD3 delta are two highly related components of the T cell receptor (TCR)-CD3 complex which is essential for the assembly and signal transduction of the T cell receptor on mature T cells. In gene knockout mice deficient in either CD3 delta or CD3 gamma, early thymic development mediated by pre-TCR was either undisturbed or severely blocked, respectively, and small numbers of TCR-alpha beta(+) T cells were detected in the periphery of both mice. gamma delta T cell development was either normal in CD3 delta(-/-) mice or partially blocked in CD3 gamma(-/-) mice. To examine the collective role of CD3 gamma and CD3 delta in the assembly and function of pre-TCR and in the development of gamma delta T cells, we generated a mouse strain with a disruption in both CD3 gamma and CD3 delta genes (CD3 gamma delta(-/-)). In contrast to mice deficient in either CD3 gamma or CD3 delta chains, early thymic development mediated by pre-TCR is completely blocked, and TCR-alpha beta(+) or TCR-gamma delta(+) T cells were absent in the CD3 gamma delta(-/-) mice. Taken together, these studies demonstrated that CD3 gamma and CD3 delta pray an essential, yet partially overlapping, role in the development of both alpha beta and gamma delta T cell lineages.