title: Role of CD4 molecule in intrathymic T-cell development.
abstract: We have investigated the role of CD4 molecules in intrathymic T-cell repertoire selection. The administration of monoclonal antibody (mAb) to CD4 in organ culture of murine foetal thymus (FTOC) completely inhibited the development of CD4+8- cells, and additional treatment with anti-class II MHC (Ia) mAb caused no further effects on this inhibition. On the other hand, when the potentially autoreactive cells in Mls-1a mice were monitored by expression of the Mls-1a-reactive V beta 6 gene product of T-cell receptor alpha beta (TcR alpha beta), the treatment with anti-CD4 resulted in the appearance of V beta 6-bearing cells to some extent, but this effect was considerably reinforced by the combinatory use of anti-Ia mAb with anti-CD4. In a model system where the bacterial superantigen staphylococcal enterotoxin B serves as self-antigen to deplete V beta 8-bearing cells in FTOC, the depletion of V beta 8+ cells was restored partially by anti-CD4 alone but completely by the combination with anti-Ia. These results suggest that CD4 is indispensable for positive selection of all CD4+8- thymocytes, whereas participation of CD4 in negative selection is only partial. It was also observed that the development of TcR alpha beta-bearing cells in the CD4-8- population was inhibited by the treatment with anti-CD4 mAb. In Mls-1a mice, V beta 6-bearing cells were developed in CD4-8+, CD4+8+, and also in CD4-8- populations after anti-CD4 mAb treatment. It is suggested that TcR alpha beta-bearing CD4-8- cells are possibly originated from CD4+ cells and undergo CD4-mediated thymic selection.
authors.affiliation: Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: T
authors.initials: T
authors.lastname: Horiuchi
authors.forename: K
authors.initials: K
authors.lastname: Hamamura
authors.forename: T
authors.initials: T
authors.lastname: Sugimoto
authors.forename: H
authors.initials: H
authors.lastname: Yagita
authors.forename: K
authors.initials: K
authors.lastname: Okumura
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D051379:Mice; D008806:Mice, Inbred AKR; D008809:Mice, Inbred C3H; D009924:Organ Culture Techniques; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000196:embryology / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta