A nonsecreted variant of interleukin-4 is associated with apoptosis:: implication for the T helper-2 polarization in HIV infection

A nonsecreted variant of interleukin-4 is associated with apoptosis:: implication for the T helper-2 polarization in HIV infection
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DOI:
10.1182/blood-2002-08-2499
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发表时间:
2003-04-15
期刊:
影响因子:
20.3
通讯作者:
Gougeon, ML
Gougeon, ML
中科院分区:
医学1区
文献类型:
--
作者:
Ledru, E;Février, M;Gougeon, ML

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我们报告了一种白细胞介素4(IL-4)变异体的检测,该变异体的表达与剥夺细胞凋亡密切相关。8D4抗IL-4单抗不仅在Th2细胞中检测到,而且在Th1克隆和原代T细胞中也能检测到,它是一种非分泌性分子。在原发坏死期不表达。我们的数据表明,在剥夺细胞凋亡过程中,另一种IL-4mRNA(IL-4Delta(13))的从头转录被诱导。在HIV感染患者中,T细胞中IL-4的表达增加与细胞凋亡率的增加高度相关,仅限于8D4反应性(r(2)=0.84,在%8D4-8(+)和%7-氨基放线菌素D阳性[7-AAD(+)]外周T细胞之间,P<.0001),并与疾病进展有关。凋亡的T细胞对8D4单抗的特殊反应性可能解释了分析HIV感染中Th1/Th2平衡的研究之间的一些不一致,并质疑这种细胞内2型信号的功能。(C)2003年,由美国血液病学会提供。
We report the detection of an interieukin-4 (IL-4) variant whose expression is tightly associated with deprivation apoptosis. It is detected with the 8D4 anti-IL-4 monoclonal antibody (mAb) not only in T helper-2 (Th2) but also in Th1 clones, and primary T cells, and it is a nonsecreted molecule. It is not expressed during primary necrosis. Our data suggest that de novo IL-4 transcription of an alternative IL-4 mRNA (IL-4delta(13)) is induced during deprivation apoptosis. In HIV-infected patients, increased expression of IL-4 in T cells is highly correlated to increased apoptosis, restricted to 8D4 reactivity (r(2) = 0.84 between % 8D4-8(+) and % 7-amino-actinomycin D-positive [7-AAD(+)] peripheral T cells, P < .0001), and associated with disease progression. The particular reactivity of apoptotic T cells to 8D4 mAb may explain some discordances among studies analyzing the Th1/Th2 balance in HIV infection and questions the function of this intracellular type 2 signal. (C) 2003 by The American Society of Hematology.