CD3 components at the surface of pro‐T cells can mediate pre‐T cell development in vivo

Abstract

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.