Immature thymocytes are protected from deletion early in ontogeny

Self/non-self discrimination occurs within the thymus, where T cells undergo positive selection to produce a repertoire that recognizes foreign antigen in the context of self major histocompatibility complex proteins and negative selection to eliminate from the repertoire those T cells with self-reactive specificities. We have previously shown that two subpopulations of immature antigen receptor-bearing thymocytes exist, one that is susceptible to negative selection induced by ligation of the T-cell receptor for antigen and a second that is resistant to T-cell receptor-mediated negative selection. In the current work, we show that all antigen receptor-bearing thymocytes in early fetal thymuses are resistant to negative selection and that thymocytes susceptible to deletion do not develop until later gestational ages. Thus, deletion is a relatively late event in T-cell ontogeny. In addition, these data suggest that a thymocyte population can be isolated early in ontogeny that is capable of transducing selective signals through the antigen receptor, which do not lead to deletion but may result in positive selection.