Jones L A, Chin L T, Merriam G R, Nelson L M, Kruisbeck A M
Biological Response Modifiers Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
J Exp Med. 1990 Nov 1;172(5):1277-85. doi: 10.1084/jem.172.5.1277.
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 of autoimmune diseases in neonatally thymectomized (neoTx) mice and by the failure of clonal 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 V beta 11+ T cells in BALB/c mice and V beta 5+ and V beta 6+ 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-V beta 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 of self-reactive T cells, but self-tolerance is maintained through functional inactivation of potentially self-reactive clones.
自身耐受性部分是通过胸腺内自身反应性T细胞的清除来实现的。新生期胸腺切除（neoTx）小鼠中自身免疫性疾病的发生以及裸鼠中克隆清除的失败提示了胸腺对于这一过程的必要性。事实上，本研究表明出生后第3天进行新生期胸腺切除会导致BALB/c小鼠中Vβ11 + T细胞以及DBA/2小鼠中Vβ5 + 和Vβ6 + T细胞的克隆清除失败。然而，通过用适当的抗Vβ单克隆抗体或刺激细胞刺激后，这些潜在的自身反应性细胞在增殖和淋巴因子产生方面并无功能。似乎这种无反应性的诱导可能发生在胸腺外：早期新生胸腺（可能是在neoTx小鼠中观察到的外周T细胞的来源）也含有具有自身反应性受体的T细胞，但这些细胞功能完全正常。因此，新生期胸腺切除会中止自身反应性T细胞的清除，但通过潜在自身反应性克隆的功能失活维持了自身耐受性。
