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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >Switch from perforin-expressing to perforin-deficient CD8(+) T cells accounts for two distinct types of effector cytotoxic T lymphocytes in vivo.
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Switch from perforin-expressing to perforin-deficient CD8(+) T cells accounts for two distinct types of effector cytotoxic T lymphocytes in vivo.

机译：从表达穿孔素的CD8（+）T细胞不足的穿孔转换为体内两种不同类型的效应细胞毒性T淋巴细胞。

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Although CD8(+) cytotoxic T lymphocytes (CTL) exhibit both Fas ligand (FasL) -based and perforin-based lytic activities, the accepted hallmark of a fully active CTL remains its perforin killing machinery. Yet the origin, rationale for possessing both a slow-acting (FasL) and a fast-acting (perforin) killing mechanism has remained enigmatic. Here we have investigated perforin expression in CTL directly involved in acute tumour (i.e. leukaemias EL4 and L1210) allograft rejection occurring within the peritoneal cavity. We show that at the height of the immune response, the majority of conjugate-forming CD8(+) CTL express high levels of perforin messenger RNA and protein, and kill essentially via perforin. Later however, coinciding with complete rejection, fully cytocidal CTL emerge which exhibit a stark decrease in perforin and now kill preferentially via constitutively expressed FasL. Although late in emergence, and persistent, these powerful CTL are neither effector-memory nor memory CTL. This finding has implications for the monitoring of anti-transplant responses in clinical settings, based on assessing perforin expression in graft infiltrating CD8(+) T cells. The results show that as the immune response progresses in vivo, targeted cellular suicide mainly prunes high perforin-expressing CD8(+) cells, resulting in the gradual switch in effector CTL, from mostly perforin-based to largely Fas/FasL-based killers. Hence, two kinds of CD8(+) CTL have two killing strategies.
机译：尽管CD8（+）细胞毒性T淋巴细胞（CTL）同时具有基于Fas配体（FasL）和基于穿孔素的裂解活性，但公认的全活性CTL标志仍是其穿孔素杀伤机制。然而，同时具有缓慢作用（FasL）和快速作用（穿孔素）杀伤机制的原理仍然是个谜。在这里，我们研究了腹膜腔内异体移植排斥反应中直接参与急性肿瘤（即白血病EL4和L1210）的CTL中穿孔素的表达。我们显示，在免疫反应的高度，大多数形成偶联物的CD8（+）CTL表达高水平的穿孔素信使RNA和蛋白质，并基本上通过穿孔素杀死。然而，后来，与完全排斥反应一致，出现了完全杀细胞的CTL，其表现出穿孔素的急剧下降，现在优先通过组成型表达的FasL杀死。尽管功能强大的CTL出现较晚且持久，但它们既不是效应器记忆也不是记忆CTL。根据评估移植物浸润CD8（+）T细胞中穿孔素的表达，这一发现对临床环境中抗移植反应的监测具有重要意义。结果表明，随着体内免疫反应的发展，靶向细胞自杀主要会修剪表达高穿孔素的CD8（+）细胞，从而导致效应CTL逐渐从主要基于穿孔素的杀伤剂转变为主要基于Fas / FasL的杀伤剂。因此，两种CD8（+）CTL具有两种杀灭策略。

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