Reply to "CD8+ T cells are essential for controlling acute FV infection in B6 mice."
Reply to "CD8+ T cells are essential for controlling acute FV infection in B6 mice."
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回复“CD8 T 细胞对于控制 B6 小鼠的急性 FV 感染至关重要”。
DOI：
10.1128/jvi.00343-14
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
and M. Miyazawa
中科院分区：
文献类型：
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作者：
Tsuji-Kawahara;S.;S. Takamura;and M. Miyazawa
在题为“CD8+ T细胞对于控制C57BL/6小鼠的急性朋友逆转录病毒感染至关重要”(1)的信中，Joedicke等人对我们最近的信(2)中提出的数据的解释提出了一些问题。首先，他们指出，在β2-微球蛋白（β2m）缺乏的小鼠中，CD8+ T细胞的缺乏可能通过其他免疫细胞亚群的增强反应来补偿。为了支持这一观点，作者引用了他们最近在该杂志上发表的论文(3)，并指出CD4+ T细胞通常不会对FV感染产生细胞毒性，但在缺乏CD8+ T细胞的情况下会产生细胞毒性。然而，在CD4+ T细胞中，通过表达特异性细胞溶解分子（包括颗粒酶和穿孔素）来诱导细胞毒性功能并不是一种例外现象，但最近的一份报告表明，成熟CD4+ T细胞重编程为细胞毒性细胞具有很大程度的可塑性(4)。因此，成熟的、抗原经历的CD4+ T细胞可以终止辅助性T细胞分化的主调控因子的表达，并在慢性或强刺激下转换为细胞毒性效应细胞。事实上，我们已经证明，在有CD8+ T细胞存在的情况下，如果通过合成肽疫苗预先给FV易感小鼠接种由FV衍生的CD4+ T细胞表位，CD4+ T细胞可以对FV感染发挥细胞毒性活性(5)。此外，如果CD8+ t细胞的功能可以被其他免疫细胞的功能所取代，那么它们就不是必不可少的，而是可缺性的。Joedicke等人(1)也声称Lyt2 （CD8α）缺陷小鼠完全缺乏CD8+ T细胞，而我们使用的β m2缺陷小鼠可能具有残留的CD8+ T细胞，这可能有助于观察到的FV消除。然而，β2m缺陷小鼠的细胞表面完全缺乏主要组织相容性复合体（MHC） I类分子的表达(6)，因此，即使存在残留的CD8+ T细胞，这些细胞也不能识别病毒感染的靶细胞。相反，人们早就知道CD8协受体对MHC i类限制性T细胞的发育和效应功能并不重要。事实上，缺乏CD8α链（CD8敲除）的小鼠即使在CD4+ T细胞耗尽时也能有效地排斥MHC i类异质皮肤移植物，并且在CD8敲除受体小鼠中检测到供体细胞特异性细胞毒活性(7)。此外，野生型和CD8敲除C57BL/6 （B6）小鼠对小鼠多瘤病毒感染具有相同的抗性，而β2m缺陷小鼠则易感，并且在感染的CD8敲除小鼠中检测到CD3+ CD4 J T细胞结合带有db限制性显性多瘤病毒表位的MHC I类四聚体（8,9）。由于Joedicke等使用的CD8敲除小鼠可以产生MHC i类限制性细胞毒效应细胞，而这些细胞不能裂解i类缺陷靶细胞，我们可以得出结论，β2m缺陷小鼠比CD8敲除小鼠更适合评估i类限制性细胞毒T细胞在FV感染中的作用。
I n the letter entitled “CD8+ T Cells Are Essential for Controlling Acute Friend Retrovirus Infection in C57BL/6 Mice”(1), Joedicke et al. raised some questions about interpretations of the data presented in our recent letter (2). First, they point out that the lack of CD8+ T cells in β2-microglobulin (β2m)-deficient mice might be compensated for by enhanced responses of other immune cell subsets. To support this notion, the authors cite their recent paper in this journal (3) and state that CD4+ T cells do not normally develop cytotoxicity in response to FV infection, but do so in the absence of CD8+ T cells. However, the induction of cytotoxic functions with the expression of discriminative cytolytic molecules, including granzymes and perforin, in CD4+ T cells is not an exceptional phenomenon, but a recent report has demonstrated a large degree of plasticity in reprogramming of mature CD4+ T cells into cytotoxic cells (4). Thus, mature, antigen-experienced CD4+ T cells can terminate the expression of the master regulator of helper T-cell differentiation and switch to cytotoxic effector cells in response to chronic or strong stimulation. In fact, we have shown that CD4+ T cells can exert cytotoxic activities upon FV infection in the presence of CD8+ T cells when FV-susceptible mice are primed beforehand with an FV-derived CD4+ T-cell epitope through vaccination with a synthetic peptide (5). Further, if CD8+ T-cell functions can be replaced with those of other immune cells, they are not essential but dispensable by definition.Joedicke et al.(1) also claim that Lyt2 (CD8α)-deficient mice are completely devoid of CD8+ T cells, while the β2m-deficient mice we used may possess residual CD8+ T cells, which might have contributed to the observed FV elimination. However, cells in β2m-deficient mice totally lack the expression of major histocompatibility complex (MHC) class I molecules on their surfaces (6), and thus, even if there were residual CD8+ T cells, such cells cannot recognize virus-infected target cells. On the contrary, it has long been known that CD8 coreceptors are not crucial for the development and effector functions of MHC class I-restricted T cells. In fact, mice deficient in the CD8α chain (CD8 knockout) efficiently rejected MHC class I-disparate skin grafts even when they were depleted of CD4+ T cells, and donor cell-specific cytotoxic activity was detected in the CD8 knockout recipient mice (7). Further, wild-type and CD8 knockout C57BL/6 (B6) mice were equally resistant to mouse polyomavirus infection, while β2m-deficient mice were susceptible, and CD3+ CD4 J T cells that bound to the MHC class I tetramer loaded with a Db-restricted, dominant polyomavirus epitope were detected in infected CD8 knockout mice (8, 9). As MHC class I-restricted cytotoxic effector cells can be generated in the CD8 knockout mice Joedicke et al. used, while such cells cannot lyse class I-deficient target cells, we would conclude that β2m-deficient mice are better suited for evaluating the role of class I-restricted cytotoxic T cells in FV infection than CD8 knockout mice.