La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
J Exp Med. 2010 May 10;207(5):1015-29. doi: 10.1084/jem.20090557. Epub 2010 Apr 19.
Mouse natural killer T (NKT) cells with an invariant V alpha14-J alpha18 rearrangement (V alpha14 invariant [V alpha14i] NKT cells) are either CD4(+)CD8(-) or CD4(-)CD8(-). Because transgenic mice with forced CD8 expression in all T cells exhibited a profound NKT cell deficit, the absence of CD8 has been attributed to negative selection. We now present evidence that CD8 does not serve as a coreceptor for CD1d recognition and that the defect in development in CD8 transgene homozygous mice is the result of a reduction in secondary T cell receptor alpha rearrangements. Thymocytes from mice hemizygous for the CD8 transgene have a less severe rearrangement defect and have functional CD8(+) V alpha14i NKT cells. Furthermore, we demonstrate that the transcription factor Th, Poxviruses and Zinc finger, and Krüppel family (Th-POK) is expressed by V alpha14i NKT cells throughout their differentiation and is necessary both to silence CD8 expression and for the functional maturity of V alpha14i NKT cells. We therefore suggest that Th-POK expression is required for the normal development of V alpha14i NKT cells and that the absence of CD8 expression by these cells is a by-product of such expression, as opposed to the result of negative selection of CD8-expressing V alpha14i NKT cells.
小鼠天然杀伤 T (NKT) 细胞具有不变的 V alpha14-J alpha18 重排 (V alpha14 不变 [V alpha14i] NKT 细胞)，要么是 CD4(+)CD8(-)，要么是 CD4(-)CD8(-)。因为在所有 T 细胞中强制表达 CD8 的转基因小鼠表现出明显的 NKT 细胞缺陷，所以缺乏 CD8 归因于负选择。我们现在提供的证据表明，CD8 不作为 CD1d 识别的共受体，并且在 CD8 转基因纯合子小鼠中发育缺陷是由于次要 T 细胞受体 alpha 重排减少的结果。CD8 转基因半合子小鼠的胸腺细胞具有较轻的重排缺陷，并且具有功能性 CD8(+)V alpha14i NKT 细胞。此外，我们证明转录因子 Th、Poxviruses 和 Zinc finger、和 Krüppel 家族 (Th-POK) 在其分化过程中由 V alpha14i NKT 细胞表达，对于沉默 CD8 表达和 V alpha14i NKT 细胞的功能成熟都是必需的。因此，我们认为 Th-POK 表达是 V alpha14i NKT 细胞正常发育所必需的，而这些细胞缺乏 CD8 表达是这种表达的副产品，而不是 CD8 表达的 V alpha14i NKT 细胞的负选择的结果。
