CD3 COMPONENTS AT THE SURFACE OF PRO-T CELLS CAN MEDIATE PRE-T CELL-DEVELOPMENT IN-VIVO

Developmentally arrested pro-T cells (CD4(-)8(-), IL-2R(+), HSA(++)) of RAG-1-deficient mice appear to express low levels of CD3 molecules in the absence of T cell receptor (TcR) chains at their surface, while developmentally arrested pre-T cells of TcR alpha-deficient mice express low levels of a disulfide-linked TcR beta chain in association with CD3 molecules. Cross-linking of the CD3 modules on pro-T cells of RAG-1(-/-) mice in vivo, with either of two different CD3 epsilon-specific monoclonal antibodies, induces differentiation of these pro-T cells into pre-T cells (CD4(+)8(+), IL-2R(-), HSA(+)), concomitant with a rapid expansion of the thymic T cell compartment, up to 175-fold within 12 days. The same effects can be produced by introduction of a mutant TcR beta transgene lacking most of the variable domain (Delta V-TcR beta) into the RAG-1(-/-) background. These experiments suggest that cross-linking of the CD3 modules on pro-T cells mimics the signaling function expected of the pre-TcR complex, which is found at the surface of pre-T cells prior to functional TcR alpha gene rearrangement. The variable domain of the TcR beta chain is apparently not essential for inducing these aspects of T cell development.