Conventional, naive CD4+ T cells provide an initial source of IL-4 during Th2 differentiation
Conventional, naive CD4+ T cells provide an initial source of IL-4 during Th2 differentiation
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DOI：
10.4049/jimmunol.165.7.3620
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发表时间：
2000-10-01
影响因子：
4.4
通讯作者：
Paul, WE
中科院分区：
文献类型：
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作者：
Noben-Trauth, N;Hu-Li, J;Paul, WE
已知IL-4可促进CD4(+)T细胞分化为分泌IL-4的Th2细胞。然而，在活体内驱动Th2反应的IL-4早期爆发的细胞来源尚未确定。IL-4受体α链缺陷小鼠(IL-4Rα(-/-))保持分泌IL-4的能力，并可用于识别那些产生IL-4的细胞类型，而不需要事先IL-4介导的刺激。为了解决幼稚的、传统的CD4(+)T细胞是否可能在抗原特异性反应中最初产生IL-4的问题，我们将BALB/c IL-4Rα(-/-)小鼠与DO11.10/SCID TCR转基因小鼠杂交。野生型和IL-4Rα(-/-)DO11.10/SCID小鼠的淋巴结细胞在多肽刺激后48h内每10(6)个细胞分泌的IL-4接近50pg。这种少量的IL-4足以导致野生型CD4(+)T细胞分化为Th2细胞，特别是在启动培养过程中干扰素-γ和IL-12被中和的情况下。IL-4Rα(-/-)小鼠的CD4(+)细胞在抗-干扰素-γ和抗-IL-12的刺激下产生少量的IL-4细胞(接近2%)。这些数据表明，传统的幼稚的CD4(+)T细胞可以被认为是IL-4的初始来源，而在没有干扰素-γ和IL-12的情况下，这种IL-4可以诱导Th2极化。
IL-4 is known to promote the differentiation of CD4(+) T cells into IL-4-secreting Th2 cells. However, the cellular source of the early burst of IL-4 that drives Th2 responses in vivo has not been conclusively identified. Mice deficient for the IL-4 receptor alpha-chain (IL-4R alpha(-/-)) retain the capacity to secrete IL-4 and can be used to identify those cell types that produce IL-4 without a requirement for prior IL-4-mediated stimulation. To address whether naive, conventional CD4(+) T cells may act as initial producers of IL-4 in Ag-specific responses, we crossed the BALB/c IL-4R alpha(-/-)mice to DO11.10/scid TCR transgenic mice. Lymph node cells from wild-type and IL-4R alpha(-/-) DO11.10/scid mice secreted similar to 50 pg of IL-4 per 10(6) cells within 48 h after peptide stimulation. This small amount of IL-4 was sufficient to cause the differentiation of wild-type CD4(+) T cells into Th2 cells, particularly if IFN-gamma and IL-12 were neutralized during the priming cultures. CD4(+) cells from the IL-4R alpha(-/-) mice gave rise to a minor proportion (similar to 2%) of IL-4-producing cells upon stimulation in the presence of anti-IFN-gamma and anti-IL-12, These data show that conventional, naive CD4(+) T cells may be considered as initial sources of IL-4 and, in the absence of IFN-gamma and IL-12, this IL-4 can induce Th2 polarization.