Anergic CD4+ T cells underlying impaired immune system in leukemia

将正常幼龄B6小鼠移植白血病细胞系后，幼龄小鼠很少见到的PD-1+ CD4+ T细胞迅速而强劲地增加，CD4+ T细胞对抗cd3单抗的反应被严重抑制。PD-1+ CD4+ T细胞优先在白血病累及的淋巴组织中检测到，提示这些T细胞是白血病组织中重要的宿主成分。它们表现出与常规CD4+ T细胞不同的遗传特征，包括C/EBPα的高表达，这通常在髓系细胞中表达。使用TCR转基因小鼠作为白血病受体，我们证实PD-1+ CD4+ T细胞来源于记忆表型，而不是幼稚群体。

When normal young B6 mice were transplanted with leukemia cell lines, PD-1+ CD4+ T cells, which are hardly seen in young mice, were rapidly and robustly increased, and the response of CD4+ T cells to anti -CD3 mAb was profoundly depressed. PD-1+ CD4+ T cells were preferentially detected in the lymphoid tissues with leukemia involvement, suggesting that these T cells constituted a significant host component in leukemic tissues. They exhibited a genetic signature distinct from regular CD4+ T cells including the high expression of C/EBPα, which is normally expressed in myeloid lineage cells. Using TCR transgenic mice as recipients of leukemia, we confirmed that the PD-1+ CD4+ T cells were derived from memory phenotype, but not naive, population.