IL-7 signals are crucial for the survival of naive and memory T cells, and the IL-7R is expressed on the surface of these cells. Following viral infection, the IL-7R is expressed on only a subset of effector CD8 T cells, and has been demonstrated to be important for the survival of these memory precursors. IL-7 message levels remain relatively constant during the T cell response to lymphocytic choriomeningitis virus, but a short-lived burst of GM-CSF is observed soon after infection. Retroviral expression of a chimeric GM-CSF/IL-7R, in which binding of GM-CSF by T cells leads to IL-7 signaling, allows for the delivery of an IL-7 signal in all effector T cells expressing the receptor. In mice infected with lymphocytic choriomeningitis virus, CD8 and CD4 T cells transduced with this chimeric receptor underwent an enhanced proliferative response compared with untransduced populations in the same host. Similarly, TCR transgenic CD8 cells expressing the chimeric receptor produced higher effector numbers during the peak of the T cell response to infection. Surprisingly, the enhanced proliferation did not lead to higher memory numbers, as the subsequent contraction phase was more pronounced in the transduced cell populations. These findings demonstrate that artificial IL-7 signaling during an infection leads to significantly increased Ag-specific effector T cell numbers, but does not result in increased numbers of memory progeny. The extent of contraction may be dictated by intrinsic factors related to the number of prior cell divisions.

译文

:IL-7信号对于幼稚和记忆性T细胞的存活至关重要,而IL-7R在这些细胞的表面表达。病毒感染后,IL-7R仅在效应CD8 T细胞的一部分上表达,并已证明对这些记忆前体的存活很重要。在对淋巴细胞性脉络膜脑膜炎病毒的T细胞反应过程中,IL-7信息水平保持相对恒定,但是感染后不久就观察到了短暂的GM-CSF爆发。嵌合GM-CSF / IL-7R的逆转录病毒表达(其中T细胞与GM-CSF结合导致IL-7信号传导)允许在表达该受体的所有效应T细胞中传递IL-7信号。在感染了淋巴细胞性脉络膜脑膜炎病毒的小鼠中,用该嵌合受体转导的CD8和CD4 T细胞与同一宿主中未转导的种群相比,具有增强的增殖反应。同样,表达嵌合受体的TCR转基因CD8细胞在感染的T细胞反应高峰期间产生更高的效应子数量。出人意料的是,增强的增殖并未导致更高的记忆数,因为随后的收缩期在转导的细胞群中更为明显。这些发现表明,感染期间的人工IL-7信号转导会导致Ag特异性效应T细胞数量显着增加,但不会导致记忆后代数量增加。收缩的程度可以由与先前细胞分裂数有关的内在因素决定。

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