Intrathymic deletion of self-reactive cells prevented by neonatal anti-CD4 antibody treatment.
T-cell differentiation in the thymus involves the coordinate expression of genes encoding the alpha and beta chains of the major histocompatibility complex-restricted heterodimeric antigen receptor (TCR) complex, as well as other functionally important molecules such as CD4 and CD8. The repertoire of TCR expressed by T cells is generally thought to be influenced by positive and/or negative selection events occurring when TCRs on developing T cells interact with self-antigens and major histocompatibility complex components. Using a model system in which specific antigen-reactive cells can be monitored by virtue of their preferential expression of certain TCR beta-chain variable (V beta) domains, it has been shown that self-reactive T cells are clonally deleted during development. We report here that clonal deletion of V+ beta 6 cells in Mlsa mice can be prevented by in vivo neonatal administration of monoclonal antibodies directed against CD4. Furthermore, as anti-CD4 monoclonal antibody treatment resulted in the reappearance of V+ beta 6 cells in the mature CD8+ T-cell subset, it is likely that clonal deletion acts on the CD4+CD8+ thymocyte subset and that this subset is an intermediate stage in the differentiation pathway of both CD4+ and CD8+ T-cell lineages.
MacDonald
H R
HR
Ludwig Institute for Cancer Research, Lausanne Branch, Epalinges, Switzerland.
Hengartner
H
H
Pedrazzini
T
T
D000818:Animals; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D002454:Cell Differentiation; D051379:Mice; D008807:Mice, Inbred BALB C; D008912:Minor Histocompatibility Loci; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D011948:Receptors, Antigen, T-Cell