Jenkinson S Rhiannon, Intlekofer Andrew M, Sun Guangping, Feigenbaum Lionel, Reiner Steven L, Bosselut Rémy
Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
J Exp Med. 2007 Feb 19;204(2):267-72. doi: 10.1084/jem.20061982. Epub 2007 Feb 12.
Most T cells belong to either of two lineages defined by the mutually exclusive expression of CD4 and CD8 coreceptors: CD4 T cells are major histocompatibility complex (MHC) II restricted and have helper function, whereas CD8 T cells are MHC I restricted and have cytotoxic function. The divergence between these two lineages occurs during intrathymic selection and is thought to be irreversible in mature T cells. It is, however, unclear whether the CD4-CD8 differentiation of postthymic T cells retains some level of plasticity or is stably maintained by mechanisms distinct from those that set lineage choice in the thymus. To address this issue, we examined if coreceptor or effector gene expression in mature CD8 T cells remains sensitive to the zinc finger transcription factor cKrox, which promotes CD4 and inhibits CD8 differentiation when expressed in thymocytes. We show that cKrox transduction into CD8 T cells inhibits their expression of CD8 and cytotoxic effector genes and impairs their cytotoxic activity, and that it promotes expression of helper-specific genes, although not of CD4 itself. These observations reveal a persistent degree of plasticity in CD4-CD8 differentiation in mature T cells.
大多数T细胞属于由CD4和CD8共受体相互排斥表达所定义的两个谱系之一：CD4 T细胞受主要组织相容性复合体（MHC）II类分子限制并具有辅助功能，而CD8 T细胞受MHC I类分子限制并具有细胞毒性功能。这两个谱系之间的分化发生在胸腺内选择过程中，并且被认为在成熟T细胞中是不可逆的。然而，尚不清楚胸腺后T细胞的CD4 - CD8分化是否保留一定程度的可塑性，或者是否由与决定胸腺中谱系选择的机制不同的机制稳定维持。为了解决这个问题，我们研究了成熟CD8 T细胞中的共受体或效应基因表达是否仍然对锌指转录因子cKrox敏感，当在胸腺细胞中表达时，cKrox会促进CD4分化并抑制CD8分化。我们发现，将cKrox转导到CD8 T细胞中会抑制其CD8和细胞毒性效应基因的表达，并损害其细胞毒性活性，并且它会促进辅助特异性基因的表达，尽管不会促进CD4本身的表达。这些观察结果揭示了成熟T细胞中CD4 - CD8分化存在持续的可塑性程度。
