Evidence for the divergence of innate and adaptive T-cell precursors before commitment to the αβ and γδ lineages
Evidence for the divergence of innate and adaptive T-cell precursors before commitment to the αβ and γδ lineages
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DOI：
10.1182/blood-2011-05-352732
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发表时间：
2011-12-15
期刊：
影响因子：
20.3
通讯作者：
Kopf, Manfred
中科院分区：
文献类型：
--
作者：
Kisielow, Jan;Tortola, Luigi;Kopf, Manfred
除了适应性T细胞之外，胸腺还支持非常规T细胞的发育，例如自然杀伤T（NKT）和CD 8 α α上皮内淋巴细胞（IEL），其具有先天功能特性、特定抗原特异性和组织定位。传统T细胞和先天T细胞都被认为是从共同的前体细胞发育而来，经历了指导性的、TCR介导的谱系命运决定，但先天T细胞被认为会经历阳性选择而不是阴性选择来响应激动性TCR信号。在本研究中，我们表明，与传统的α β T细胞，先天性α β T细胞不选择对功能性TCR γ重排和表达TCR γ mRNA。同样，与大多数γ δ T细胞相反，胸腺先天γ δ T细胞不能有效地针对功能性TCR γ链进行选择。在常规T细胞的前体中，在不存在配体的情况下从前TCR或γ δ TCR发出的自主TCR信号介导针对相反同种型的TCR的选择和α β/γ δ谱系定型。我们的数据表明，发育中的先天性T细胞忽略了这些信号，只依赖于激动性TCR相互作用。一致地，大多数先天性T细胞对自体胸腺细胞反应强烈。这些结果表明，先天性和适应性T细胞谱系不从相同的前体池发展，并且在α β/γ δ谱系定型之前可能发生分歧。（血。2011;118（25）：6591-6600）
In addition to adaptive T cells, the thymus supports the development of unconventional T cells such as natural killer T (NKT) and CD8 alpha alpha intraepithelial lymphocytes (IELs), which have innate functional properties, particular antigenic specificities, and tissue localization. Both conventional and innate T cells are believed to develop from common precursors undergoing instructive, TCR-mediated lineage fate decisions, but innate T cells are proposed to undergo positive instead of negative selection in response to agonistic TCR signals. In the present study, we show that, in contrast to conventional alpha beta T cells, innate alpha beta T cells are not selected against functional TCR gamma rearrangements and express TCR gamma mRNA. Likewise, in contrast to the majority of gamma delta T cells, thymic innate gamma delta T cells are not efficiently selected against functional TCR gamma chains. In precursors of conventional T cells, autonomous TCR signals emanating from the pre-TCR or gamma delta TCR in the absence of ligand mediate selection against the TCR of the opposite isotype and alpha beta/gamma delta lineage commitment. Our data suggest that developing innate T cells ignore such signals and rely solely on agonistic TCR interactions. Consistently, most innate T cells reacted strongly against autologous thymocytes. These results suggest that innate and adaptive T-cell lineages do not develop from the same pool of precursors and potentially diverge before alpha beta/gamma delta lineage commitment. (Blood. 2011;118(25):6591-6600)