Hegel Johannes K, Knieke Karin, Kolar Paula, Reiner Steven L, Brunner-Weinzierl Monika C
Department of Pediatrics, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.
Eur J Immunol. 2009 Mar;39(3):883-93. doi: 10.1002/eji.200838770.
CD8(+) T lymphocytes are required for effective host defense against pathogens and also for mediating effector responses against uncontrolled proliferating self-tissues. In this study, we determine that individual CD8(+) T cells are tightly controlled in their effector functions by CD152 (CTLA-4). We demonstrate that signals induced by CD152 reduce the frequency of IFN-gamma and granzyme B expressing CD8(+) T cells independently of the transcription factors T-bet or cKrox by selectively inhibiting accumulation of Eomesodermin mRNA and protein. Ectopic expression of Eomesodermin reversed the CD152-mediated inhibition of effector molecule production. Additionally, enhanced cytotoxicity of individual CD8(+) T cells differentiated in the absence of CD152 signaling was determined in vivo. These novel insights extend our understanding of how immune responses of CD8(+) T cells are selectively modulated.
CD8(+) T淋巴细胞对于宿主有效抵御病原体以及介导针对不受控制的自身组织增殖的效应反应至关重要。在本研究中，我们确定单个CD8(+) T细胞的效应功能受到CD152（CTLA-4）的严格调控。我们证明，CD152诱导的信号通过选择性抑制Eomesodermin mRNA和蛋白质的积累，独立于转录因子T-bet或cKrox，降低表达IFN-γ和颗粒酶B的CD8(+) T细胞的频率。Eomesodermin的异位表达逆转了CD152介导的效应分子产生的抑制作用。此外，在体内确定了在没有CD152信号传导的情况下分化的单个CD8(+) T细胞的细胞毒性增强。这些新见解扩展了我们对CD8(+) T细胞免疫反应如何被选择性调节的理解。
