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J. Exp. Med., Volume 188, Number 7, October 5, 1998 1375-1380

Essential and Partially Overlapping Role of CD3gamma and CD3delta for Development of alpha beta and gamma delta T Lymphocytes

By Baoping Wang,* Ninghai Wang,* Mariolina Salio,* Arlene Sharpe, Deborah Allen,* Jian She,* and Cox Terhorst*

From the * Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215; and the Dagger  Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115

CD3gamma and CD3delta 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 CD3delta or CD3gamma , 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 CD3delta -/- mice or partially blocked in CD3gamma -/- mice. To examine the collective role of CD3gamma and CD3delta 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 CD3gamma and CD3delta genes (CD3gamma delta -/-). In contrast to mice deficient in either CD3gamma or CD3delta 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 CD3gamma delta -/- mice. Taken together, these studies demonstrated that CD3gamma and CD3delta play an essential, yet partially overlapping, role in the development of both alpha beta and gamma delta T cell lineages.

Key words: CD3gamma CD3delta T cell receptor-CD3 complexT cell developmentknockout mouse


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