Reply to Vicetti Miguel et al., "Setting Sights on Chlamydia Immunity's Central Paradigm: Can We Hit a Moving Target?".
Reply to Vicetti Miguel et al., "Setting Sights on Chlamydia Immunity's Central Paradigm: Can We Hit a Moving Target?".
复制标题
回复 Vitti Miguel 等人，“着眼于衣原体免疫的中心范式：我们能击中移动目标吗？”。
DOI：
10.1128/iai.00223-17
复制
发表时间：
2017
影响因子：
3.1
通讯作者：
Brunham,RobertC
中科院分区：
文献类型：
--
作者：
Johnson,RaymondM;Brunham,RobertC
我们赞赏Vicetti Miguel等人的深思熟虑的评论。撰写评论的主要目的之一是引发讨论，而评论的最佳时机是长期持有的范例开始看起来有点摇摇欲坠的时刻。我们不反对评论家在现有的Th1、-2、-17的背景下对现有文学的批评……(I)白介素13(IL-13)不是唯一的Th2细胞因子，GATA3也不是Th2细胞所独有的。在已发表的文献中，来自系统性硬化症(SSC)和结核病患者的CD8T细胞同时产生干扰素和IL-13，并表达GATA3。根据不完全信息，在SSC中，相关的GATA3转录因子很可能是T-bet(1)，在结核病中，可能是eome(2)。在任何情况下，细胞因子极化的相互排他性规则在体内似乎并不是牢不可破的。表1显示了我们在2012年发表的一项研究中获得的四个多功能衣原体特异性Th1克隆(uvmo-2、uvmo-3、uvmo-4和pl4-10)的基因表达微阵列数据(3)。这些数据没有在论文中讨论，但已在基因表达总览数据库中公开获得，登录号为GSE32128。这些衣原体特异性CD4T细胞克隆产生丰富的干扰素-1，具有高信号的T-bet(Tbx21)和GATA3，而基本上不表达RORT(RORC)和Ahr。在4个克隆中的1个克隆(116个任意单位)中，有1个克隆的Eome mRNA呈弱阳性。我们特别知道4uvmo-3有显著的GATA3mRNA，产生大量的干扰素-，不产生IL-5或IL-13(我们没有专门检查IL-4)。我们有更多未发表的数据来解决这些问题，与上面讨论的细胞因子可塑性一致。(Ii)产生IL-4的循环CD4T细胞的存在并不等于保护。在对商业性工作者的研究中，我们没有观察IL-4的反应，但我们确实观察了IL-5(促进嗜酸性粒细胞增多的Th2细胞因子)，而且它与抵抗再次感染无关。
We appreciate the thoughtful comments of Vicetti Miguel et al. One of the main purposes of writing a review is to generate a discussion, and optimal times for reviews are moments where long held paradigms begin to look a little shaky. We do not disagree with the commentators’ critique of the existing literature in the context of the existing Th1,-2,-17... framework, except that there are newer T cell lineage data that show the following.(i) Interleukin-13 (IL-13) is not uniquely a Th2 cytokine, and Gata3 is not unique to Th2 cells. In the published literature, CD8 T cells from patients with systemic sclerosis (SSc) and tuberculosis make both gamma interferon (IFN-) and IL-13 and express Gata3. On the basis of incomplete information, in SSc, the relevant Gata3 partner transcription factor is likely T-bet (1), in tuberculosis, perhaps Eomes (2). In any case, the mutual exclusivity rules for cytokine polarization do not appear inviolate in vivo. Table 1 shows gene expression microarray data for four multifunctional Chlamydia-specific Th1 clones (uvmo-2, uvmo-3, uvmo-4, and spl4-10) that we obtained in a study published in 2012 (3). These data were not discussed in that paper but are publically available in the Gene Expression Omnibus database under accession number GSE32128.These Chlamydia-specific CD4 T cell clones made abundant IFN-, had high mRNA signals for T-bet (Tbx21) and Gata3, and were essentially negative for RORT (Rorc) and Ahr. There was a low positive Eomes mRNA signal in one of the four clones (116 arbitrary units). We know specifically that 4uvmo-3 has significant Gata3 mRNA, produces large amounts of IFN-, and does not produce IL-5 or IL-13 (we did not specifically check for IL-4). We have additional unpublished data addressing these issues consistent with the cytokine plasticity discussed above.(ii) The presence of circulating CD4 T cells that make IL-4 does not equal protection. We did not look at IL-4 responses during our study of commercial sex workers, but we did look at IL-5 (the Th2 cytokine that promotes eosinophilia), and it was not associated with resistance to reinfection.