OX40 costimulation enhances interleukin-4 (IL-4) expression at priming and promotes the differentiation of naive human CD4+ T cells into high IL-4-producing effectors
OX40 costimulation enhances interleukin-4 (IL-4) expression at priming and promotes the differentiation of naive human CD4+ T cells into high IL-4-producing effectors
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DOI：
10.1182/blood.v92.9.3338.421k19_3338_3345
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发表时间：
1998-11-01
期刊：
影响因子：
20.3
通讯作者：
Delespesse, G
中科院分区：
文献类型：
--
作者：
Ohshima, Y;Yang, LP;Delespesse, G
Th2细胞的发育严重依赖于启动时白细胞介素-4 （IL-4）的存在，细胞起源和在幼稚t细胞启动时调节IL-4早期产生的机制被广泛研究。我们之前报道过，抗cd3激活和cd28共刺激的初始人CD4(+) T细胞本身释放非常低但足够水平的IL-4，以支持它们向高IL-4生成细胞的发展。我们在这里表明，在活化的脐带血CD4(+) T细胞上结痂OX40 Ag（肿瘤坏死因子受体（TNF-R）家族成员），在启动时上调IL-4的产生，从而促进它们发育成效应细胞，产生高水平的2型细胞因子IL-4、IL-5和IL-13。在抗cd3 /B7.1激活48小时后，OX40结扎使IL-4 mRNA的表达增加4倍，并显著增加原代培养中IL-4和IL-13的释放。OX40共刺激对Th细胞分化的影响是在最佳和次优CD28刺激下观察到的，由于OX40配体在树突状细胞上表达，OX40共刺激途径可能通过增强il -4生成细胞的分化参与Th细胞发育的生理调节。(C) 1998年由美国血液病学会出版。
Th2 cell development is critically dependent on the presence of interleukin-4 (IL-4) at priming, The cellular origin and the mechanisms regulating this early production of IL-4 at the site of naive T-cell priming are extensively investigated. We previously reported that anti-CD3-activated and CD28-costimulated naive human CD4(+) T cells themselves release very low but sufficient levels of IL-4 to support their development into high IL-4-producing cells. We show here that ligation of OX40 Ag, a member of the tumor necrosis factor receptor (TNF-R) family, on activated umbilical cord blood CD4(+) T cells upregulates IL-4 production at priming and thereby promotes their development into effector cells producing high levels of the type 2 cytokines IL-4, IL-5, and IL-13, OX40 ligation increases four times the expression of IL-4 mRNA after 48 hours of anti-CD3/B7.1 activation and significantly augments the release of IL-4 and IL-13 in primary cultures. The effects of OX40 costimulation on Th cell differentiation are observed in the presence of optimal and suboptimal CD28 stimulation, Because OX40 ligand is expressed on dendritic cells, the OX40 costimulation pathway may be involved in the physiological regulation of Th cell development by augmenting the differentiation of IL-4-producing cells. (C) 1998 by The American Society of Hematology.