Antibodies against the T cell receptor/CD3 complex interfere with distinct intra-thymic cell-cell interactions in vivo: correlation with arrest of T cell differentiation.
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 beta 8 family) and anti-CD3 (epsilon 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.
Kyewski
B A
BA
Institute for Immunology and Genetics, German Cancer Research Center, Heidelberg, FRG.
Schirrmacher
V
V
Allison
J P
JP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D017252:CD3 Complex; D002450:Cell Communication; D002454:Cell Differentiation; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007140:Immunoglobulin Fab Fragments; D011948:Receptors, Antigen, T-Cell