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.
Jacobs
H
H
Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam.
Vandeputte
D
D
Tolkamp
L
L
de Vries
E
E
Borst
J
J
Berns
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017252:CD3 Complex / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D018398:Homeodomain Proteins; D051379:Mice; D011506:Proteins / Q000032:analysis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000235:genetics; D013601:T-Lymphocytes / Q000502:physiology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D018398:Homeodomain Proteins; D011506:Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C064658:RAG-1 protein