Intrathymic deletion of self-reactive cells prevented by neonatal anti-CD4 antibody treatment

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Abstract
T-cell differentiation in the thymus involves the coordinate expression of genes encoding the α and β 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 components1. Using a model system in which specific antigen-reactive cells can be monitored by virtue of their preferential expression of certain TCR β -chain variable (Vβ) domains, it has been shown2–4 that self-reactive T cells are clonally deleted during development. We report here that clonal deletion of V+β6 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+β6 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.