FAILURE OF CLONAL DELETION IN NEONATALLY THYMECTOMIZED MICE - TOLERANCE IS PRESERVED THROUGH CLONAL ANERGY

Self-tolerance is achieved in part through intrathymic deletion of self-reactive T cells. The necessity of the thymus for this process is suggested by the development ofautoimmune diseases in neonatally thymectomized (neoTx) mice and by the failure ofclonal deletion in nude mice. Indeed, the present study demonstrates that neonatal thymectomy on day 3 after birth results in the failure of clonal deletion of Vβ11+ T cells in BALB/c mice and Vβ5+ and Vβ6+ T cells in DBA/2 mice. However, these potentially autoreactive cells are nonfunctional as measured by proliferation and lymphokine production after stimulation with appropriate anti-Vβ mAbs or stimulator cells. It appears that this induction of nonresponsiveness may have occurred extrathymically : the early neonatal thymus (presumably the source of the peripheral T cells observed in neoTx mice) also contains T cells with self-reactive receptors, but these cells are fully functional. Therefore, neonatal thymectomy aborts deletion ofself-reactive T cells, but self-tolerance is maintained through functional inactivation of potentially self-reactive clones. © 1990, Rockefeller University Press., All rights reserved.