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 TcRα‐deficient mice express low levels of a disulfide‐linked TcRβ 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′‐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 TcRβ transgene lacking most of the variable domain (ΔV‐TcRβ) 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 TcRa gene rearrangement. The variable domain of the TcRβ chain is apparently not essential for inducing these aspects of T cell development.