Influence of IL12 on the maturation of human naive T cells.
Influence of IL12 on the maturation of human naive T cells.
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IL12 对人初始 T 细胞成熟的影响。
DOI：
10.1016/0923-2494(96)83016-1
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
D. Byun
中科院分区：
文献类型：
--
作者：
G. Delespesse;C. Wu;U. Shu;D. Byun
在小鼠体内的研究已经证实，IL12在CD4T细胞亚群的分化中起着至关重要的作用。因此，在免疫时给予IL-2或抗-IL-12抗体将预期的Th细胞表型从Th2转变为Th1或相反(Heinzel等人，1993；Sypek等人，1993；M&Night等人，1994)。来自IL12处理的动物的CD4T细胞不仅产生更多的IFNy，而且它们产生IL4和IL5的能力也显著降低。体外研究表明，IL12直接作用于未成熟的T细胞，并使它们产生IFNy；然而，这些研究未能解释为什么来自IL12处理的动物的CD4T细胞不产生ILAIILS。事实上，在没有外源IL4的情况下体外启动后，启动的细胞在重新刺激时要么不产生IL4，要么只产生少量的IL4(Hsieh等人，1993；Seder等人，1993)。此外，当IL4和IL12同时存在时，IL12并不抑制IL4对IL4的产生，而IL4至少部分抑制了IL12对IFNy的促进作用。IL12在免疫反应诱导阶段的强大活性表明，这种细胞因子可能是一种非常有效的佐剂，用于接种几种细胞内病原体(Afonso等人，1994)。最近的研究(Nabors等人，1995)进一步表明，通过将Th细胞表型从促进疾病的2型转变为保护型1，IL12也可能与抗菌药物一起作为佐剂用于已建立的慢性病的治疗。IL12具有改变已建立的免疫反应的Th2/Th1平衡的潜力是由Romagnani的研究小组在人类系统中首次提出的(Manetti等人，1993)。他们报告说，IL12将特应性捐赠者的过敏原特异性T细胞的体外回忆反应从Th2表型转换为Th1样表型。在IL-12刺激的PBMC培养中加入IL-12可导致T细胞系产生明显减少的IL-4和显著增加的IFNy水平。有趣的是，IL12的这些作用是不依赖于IFNy的，但在很大程度上依赖于启动培养中NK细胞的存在。在IL12存在下重新刺激的PBMC批量培养的T细胞克隆也显示出Thl样轮廓，而来自新鲜分离的PBMC的T细胞克隆在IL12存在的情况下立即在有限稀释中培养出来的T细胞克隆显示出正常的IL4产生能力，但增加了产生IFNy的能力。我们检测了外源性IL-12对人原始CD4和CD8 T细胞分化为产生IL-4、IL-5和IFNy效应细胞的能力的影响。
In vivo studies in the mouse system have established that IL12 plays an essential role in the differentiation of CD4 T-cell subsets. Thus, administration of IL1 2 or anti-IL12 Ab at the time of immunization shifted the expected Th cell phenotype from Th2 to Thl or reciprocally (Heinzel et al., 1993; Sypek et al., 1993; M&night et al., 1994). CD4 T cells from IL12-treated animals not only produced much more IFNy, but they also displayed a markedly reduced capacity for producing IL4 and IL5 In vitro studies revealed that IL12 acts directly on naive T cells and primes them for IFNy production; however, these studies failed to explain why CD4 T cells from IL12-treated animals do not produce ILAIILS. Indeed, after in vitro priming in the absence of exogenous IL4, primed cells either did not produce or produced only little amounts of IL4 on restimulation (Hsieh et al., 1993; Seder et al., 1993). Moreover, when primed in the presence of both IL4 and IL12, IL12 did not suppress IL4 priming for IL4 production, whereas IL4 suppressed at least partly the enhancing effect of IL12 on IFNy production. The potent activity of IL12 at the induction phase of the immune response suggests that this cytokine may be a very efficient adjuvant in vaccination against several intracellular pathogens (Afonso et al., 1994). Most recent studies (Nabors et aE., 1995) further suggested that IL12 might also serve as an adjuvant, together with antimicrobial drugs, for the treatment of established chronic diseases, by converting the Th cell phenotype from a disease-promoting type 2 to a protective type 1. That IL12 has the potential to alter the Th2/Thl balance of an established immune response was first suggested in the human system by Romagnani’s group (Manetti et al., 1993). They reported that IL12 switches the in vitro recall response of allergen-specific T cells of atopic donors from Th2 to Thl-like phenotype. Addition of IL12 to PBMC cultures stimulated with IL12 leads to the generation of T-cell lines producing markedly reduced amounts of IL4 and significantly increased levels of IFNy. Interestingly, these effects of IL12 were IFNy-independent but were largely dependent upon the presence of NK cells in the priming cultures. Whereas T-cell clones derived from bulk cultures of PBMC restimulated in the presence of IL12 also display a Thllike profile, T-cell clones derived from freshly isolated PBMC that are immediately cultured in limiting dilution in the presence of IL12 display a normal IL4-producing capacity but an increased IFNy-producing capacity. We have examined the effect of exogenous IL12 on the ability of human naive CD4 and CD8 T cells to differentiate into IL4, IL5 and IFNy-producing effector cells.
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影响因子：
4.4
作者：
J. Marshall;H. Secrist;R. DeKruyff;S. Wolf;D. Umetsu
通讯作者：
J. Marshall;H. Secrist;R. DeKruyff;S. Wolf;D. Umetsu
IL-12 对体内辅助 T 细胞依赖性免疫反应的影响。
DOI：
--
发表时间：
1994
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
McKnight,AJ;Zimmer,GJ;Fogelman,I;Wolf,SF;Abbas,AK
通讯作者：
Abbas,AK
IL-12 通过作用于抗原呈递细胞来抑制匙孔血蓝蛋白引发的 CD4 T 细胞中 IL-4 的合成。
DOI：
--
发表时间：
1995
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
DeKruyff,RH;Fang,Y;Wolf,SF;Umetsu,DT
通讯作者：
Umetsu,DT
影响因子：
56.9
作者：
HSIEH, CS;MACATONIA, SE;MURPHY, KM
通讯作者：
MURPHY, KM