Three day neonatal thymectomy selectively depletes NK1.1+ T cells
Three day neonatal thymectomy selectively depletes NK1.1+ T cells
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DOI：
10.1093/intimm/10.10.1491
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发表时间：
1998-10-01
影响因子：
4.4
通讯作者：
Godfrey, D
中科院分区：
文献类型：
--
作者：
Hammond, K;Cain, W;Godfrey, D
新生儿胸腺切除术小鼠出生后3天，而不是出生时导致T细胞介导的，器官特异性的，以菌株依赖的方式自身免疫性疾病。在这种模型中导致疾病的机制尚不清楚，但答案可能在于胸腺依赖细胞或因子的缺乏。一个候选是相对罕见的NK1.1(+) T细胞（NKT细胞）群体。传统的α - β TCR+ T细胞从胚胎发生的第17-18天开始出现在胸腺中，并在出生前后开始向外周迁移，而NKT细胞的发育被认为至少延迟到出生后1周。我们已经在（BALB/c x C57BL/6）F-1（自身免疫易感）和C57BL/6（自身免疫抵抗）小鼠中证实了这种情况。此外，在新生儿胸腺切除3天后，对小鼠的T细胞（脾脏、淋巴结、肝脏和骨髓）进行检查，发现所有组织中NKT细胞的存在都显著减少。然而，与C57BL/6小鼠相比，（BALB/c x C57BL/6）F-1的耗散程度通常更为明显，并且C57BL/6小鼠中剩余的少量NKT细胞富集了胸腺中缺失的CD4(-)CD8（int）亚群，可能代表了胸腺独立的NKT细胞的独特谱系。鉴于越来越多的证据表明NKT细胞在保护自身免疫性疾病中的作用，新生儿胸腺切除术特异性去除它们可能有助于这些小鼠对自身免疫性疾病的易感性。
Neonatal thymectomy of mice 3 days after birth but not at birth leads to T cell-mediated, organ-specific, autoimmune disease in a strain-dependent manner. The mechanisms that lead to disease in this model remain unknown, but the answer may lie in a deficiency of thymus-dependent cells or factors. One candidate is the relatively rare population of NK1.1(+) T cells (NKT cells). Conventional alpha beta TCR+ T cells appear in the thymus from days 17-18 of embryogenesis and start emigrating to the periphery around birth, whereas the development of NKT cells is thought to be delayed until at least 1 week after birth. We have confirmed this to be the case in both (BALB/c x C57BL/6)F-1 (autoimmune susceptible) and C57BL/6 (autoimmune resistant) mice. Moreover, examination of T cells (in spleen, lymph nodes, liver and bone marrow) from mice following 3 day neonatal thymectomy revealed a significant reduction in the presence of NKT cells in all tissues. However, the extent of depletion was generally more pronounced in (BALB/c x C57BL/6)F-1 than in C57BL/6 mice, and the few remaining NKT cells in C57BL/6 mice were enriched for a CD4(-)CD8(int) subset which is absent from the thymus and may represent a distinct lineage of thymus-independent NKT cells. Given mounting evidence of a role for NKT cells in protection from autoimmune disease, it is possible that their specific removal by neonatal thymectomy may contribute to the susceptibility of these mice to autoimmune disease.