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

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 (V_β) domains, it has been shown^2–4 that self-reactive T cells are clonally deleted during development. We report here that clonal deletion of V⁺_β6 cells in Mls^a 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.