Cyclosporin A and anti-Ia antibody cause a maturation defect of CD4+8- cells in organ-cultured fetal thymus.
The effects of anti-Ia antibodies and cyclosporin A (CsA) on phenotypic differentiation of murine thymocytes were assessed in organ-cultured fetal thymuses. Both agents specifically abrogated the generation of CD4+8- thymocytes. Immunohistochemical studies revealed that Ia antigen on the organ-cultured thymic epithelial cells did not disappear with the addition of the agents, although anti-Ia antibody was proved to bind to Ia antigen during the culture. On the other hand, CsA neither changed the expression of Ia nor bound to it. As CsA is known to block the signalling cascade initiated by perturbation of T-cell receptor (TcR), it is suggested that both the Ia expression in the thymus and the signalling via receptors on thymocytes, the signals presumably generated by TcR binding to class II MHC molecules, might be necessary for phenotypic differentiation of class II MHC-restricted T cells (CD4+8- cells), but not for class I MHC-restricted T cells (CD4-8+).
Takeuchi
Y
Y
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Habu
S
S
Okumura
K
K
Suzuki
G
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D003524:Cyclosporins / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D051379:Mice; D009924:Organ Culture Techniques; D013601:T-Lymphocytes / Q000145:classification / Q000166:cytology* / Q000187:drug effects; D013950:Thymus Gland / Q000196:embryology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D003524:Cyclosporins; D000949:Histocompatibility Antigens Class II