Suzuki H, Shinkai Y, Granger L G, Alt F W, Love P E, Singer A
Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA.
J Exp Med. 1997 Jul 7;186(1):17-23. doi: 10.1084/jem.186.1.17.
As a consequence of positive selection in the thymus, immature CD4(+)8(+) double-positive, [DP] thymocytes selectively terminate synthesis of one coreceptor molecule and, as a result, differentiate into either CD4(+) or CD8(+) T cells. The decision by individual DP thymocytes to terminate synthesis of one or the other coreceptor molecule is referred to as lineage commitment. Previously, we reported that the intrathymic signals that induced commitment to the CD4 versus CD8 T cell lineages were markedly asymmetric. Notably, CD8 commitment appeared to require lineage-specific signals, whereas CD4 commitment appeared to occur in the absence of lineage-specific signals by default. Consequently, it was unclear whether CD4 commitment, as revealed by selective termination of CD8 coreceptor synthesis, occurred in all DP thymocytes, or whether CD4 commitment occurred only in T cell receptor (TCR)-CD3-signaled DP thymocytes. Here, we report that selective termination of CD8 coreceptor synthesis does not occur in DP thymocytes spontaneously. Rather, CD4 commitment in DP thymocytes requires signals transduced by either CD3 or zeta chains, which can signal CD4 commitment even in the absence of clonotypic TCR chains.
作为胸腺中阳性选择的结果，未成熟的CD4(+)8(+)双阳性（[DP]）胸腺细胞选择性地终止一种共受体分子的合成，结果分化为CD4(+)或CD8(+) T细胞。单个DP胸腺细胞决定终止一种或另一种共受体分子的合成被称为谱系定向。此前，我们报道诱导向CD4与CD8 T细胞谱系定向的胸腺内信号明显不对称。值得注意的是，CD8定向似乎需要谱系特异性信号，而CD4定向似乎在默认情况下在没有谱系特异性信号时发生。因此，尚不清楚如通过CD8共受体合成的选择性终止所揭示的CD4定向是否发生在所有DP胸腺细胞中，或者CD4定向是否仅发生在T细胞受体（TCR）-CD3信号转导的DP胸腺细胞中。在此，我们报道DP胸腺细胞不会自发地发生CD8共受体合成的选择性终止。相反，DP胸腺细胞中的CD4定向需要由CD3或ζ链转导的信号，即使在没有克隆型TCR链的情况下，这些信号也能引发CD4定向。
