Antibodies against the T cell receptor/CD3 complex interfere with distinct intra-thymic cell-cell interactionsin vivo: correlation with arrest of T cell differentiation

Abstract

Postnatal treatment of mice with antibodies against the T cell receptor complex (TcR) prevents the differentiation of mature T cells in the thymic medulla without affecting the generation of most immature cortical thymocytes, thus interfering with a discrete stage of intra‐thymic T cell differentiation at the cortex/medulla transition. This result has been interpreted as indicating a direct role of the TcR in the differentiation of immature to mature T cells, possibly via TcR‐ligand interactions during direct cell‐cell contact. Here we analyze the effect of anti‐TcR (V_β8 family) and anti‐CD3 (ε chain) antibodies on distinct intra‐thymic cell‐cell interactions in vivo. We find that the maturation arrest of thymocytes correlates with a nearly complete abrogation of interactions of corresponding immature thymocyte with I‐A/E⁺ cortical epithelial cells and I‐A/E⁺ medullary dendritic cells, while preserving interactions with adherent I‐A/E⁻ macrophages. It is proposed that the blockade of thymocyte‐epithelial cell recognition in the cortex by anti‐TcR antibodies prevents the translocation of thymocytes into the medulla and their subsequent differentiation and selection, including interactions with dendritic cells. Interestingly, the anti‐CD3 mAb treatment seems to spare the intra‐thymic development of the CD3⁺, CD4⁻/CD8⁻ T cell lineage.