Rutishauser Rachel L, Martins Gislâine A, Kalachikov Sergey, Chandele Anmol, Parish Ian A, Meffre Eric, Jacob Joshy, Calame Kathryn, Kaech Susan M
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Immunity. 2009 Aug 21;31(2):296-308. doi: 10.1016/j.immuni.2009.05.014. Epub 2009 Aug 6.
During acute infections, a small population of effector CD8(+) T cells evades terminal differentiation and survives as long-lived memory T cells. We demonstrate that the transcriptional repressor Blimp-1 enhanced the formation of terminally differentiated CD8(+) T cells during lymphocytic choriomeningitis virus (LCMV) infection, and Blimp-1 deficiency promoted the acquisition of memory cell properties by effector cells. Blimp-1 expression was preferentially increased in terminally differentiated effector and "effector memory" (Tem) CD8(+) T cells, and gradually decayed after infection as central memory (Tcm) cells developed. Blimp-1-deficient effector CD8(+) T cells showed some reduction in effector molecule expression, but primarily developed into memory precursor cells that survived better and more rapidly acquired several Tcm cell attributes, including CD62L and IL-2 expression and enhanced proliferative responses. These results reveal a critical role for Blimp-1 in controlling terminal differentiation and suppressing memory cell developmental potential in effector CD8(+) T cells during viral infection.
在急性感染期间，一小部分效应性CD8(+) T细胞逃避终末分化，并作为长寿记忆T细胞存活下来。我们证明，转录抑制因子Blimp-1在淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染期间增强了终末分化CD8(+) T细胞的形成，而Blimp-1缺陷促进了效应细胞获得记忆细胞特性。Blimp-1表达在终末分化的效应细胞和“效应记忆”（Tem）CD8(+) T细胞中优先增加，并在感染后随着中枢记忆（Tcm）细胞的发育而逐渐衰减。Blimp-1缺陷的效应性CD8(+) T细胞在效应分子表达上有所降低，但主要发育为记忆前体细胞，这些细胞存活得更好，并更快地获得了几种Tcm细胞特性，包括CD62L和IL-2表达以及增强的增殖反应。这些结果揭示了Blimp-1在病毒感染期间控制效应性CD8(+) T细胞的终末分化和抑制记忆细胞发育潜能方面的关键作用。
