Central tolerance: Clonal deletion or clonal arrest?

Studies in various experimental animals have shown that developing T cells with specificity for self antigens can be prevented from maturation at an early stage of development. While several in vitro and in vivo experiments have shown that the mechanism of silencing autospecific T cells is the deletion of immature CD4⁺8⁺ thymocytes other experiments were interpreted to indicate that tolerance could also result from developmental arrest of more immature CD4^?8⁺ thymocytes not involving cell death. Here we show that immature CD4^?8⁺ cells when confronted with T cell receptor ligands in vitro neither survive nor differentiate into cells which cannot be deleted, indicating that clonal elimination rather than developmental arrest is the mechanism of central tolerance of all immature T cells.