Induction of Th2 cell differentiation in the primary immune response:: dendritic cells isolated from adherent cell culture treated with IL-10 prime naive CD4+ T cells to secrete IL-4
Induction of Th2 cell differentiation in the primary immune response:: dendritic cells isolated from adherent cell culture treated with IL-10 prime naive CD4+ T cells to secrete IL-4
复制标题
DOI：
10.1093/intimm/10.8.1017
复制
发表时间：
1998-08-01
影响因子：
4.4
通讯作者：
Weiner, HL
中科院分区：
文献类型：
--
作者：
Liu, LM;Rich, BE;Weiner, HL
大量观察结果表明，暴露于IL-4对于T（h）2型效应T细胞的引发是必需的，暴露于IL-12对于T（h）1型效应T细胞的引发是必需的。然而，IL-4在早期免疫应答中的最初来源尚未明确，树突状细胞（DC）是启动初始T细胞的最有效的抗原呈递细胞（APC）。在本报告中，我们发现，DC暴露于IL-10可能在IL-4分泌细胞的早期免疫应答中起重要作用，DC分离自脾贴壁细胞培养物，用rIL-10处理，（IL-10-DC）致敏的初始卵清蛋白（OVA）-TCR转基因T细胞在用OVA和脾APC再刺激后分泌IL-4。相反，从rIL-12分离的DC，rIL-4或对照处理的培养物几乎仅诱导T（h）1型效应T细胞。在IL-10-DC加初始CD 4（+）T细胞的原代培养物中检测到IL-4分泌，并且IL-10-DC对IL-4分泌T细胞的引发依赖于引发培养物中的内源性IL-4产生，因为抗IL-4中和抗体完全废除了IL-4分泌细胞的引发，抗B7 -2而非抗B7 -1抑制IL-10-DC引发T细胞分泌IL-4的能力。此外，IL-10 DC对IL-4分泌性T细胞的致敏能力与DC在原代培养物中对CD 40配体介导的IL-12 p70产生的下调密切相关，并且通过向致敏培养物中加入外源性IL-12而显著降低。因此，我们的研究结果表明，驱动T（h）2分化的早期免疫事件涉及IL-10对DC的影响。
A number of observations indicate that exposure to IL-4 is essential for the priming of T(h)2-type effector T cells and that exposure to IL-12 is essential for the priming of T(h)1-type effector T cells. However, the initial source of IL-4 in the early immune response has not been clearly identified, Dendritic cells (DC) are the most potent antigen-presenting cells (APC) in priming naive T cells. In this report, we show that DC exposed to IL-10 may play an important role in the priming of IL-4-secreting cells in the early immune response, DC isolated from splenic adherent cell cultures treated with rIL-10 (IL-10-DC) primed naive ovalbumin (OVA)-TCR transgenic T cells to secrete IL-4 upon re-stimulation with OVA and splenic APC, By contrast, DC isolated from rIL-12, rIL-4 or control treated cultures induced almost exclusively T(h)1-type effector T cells. IL-4 secretion was detected in the primary cultures of IL-10-DC plus naive CD4(+) T cells and the priming of IL-4-secreting T cells by IL-10-DC was dependent on endogenous IL-4 production in the priming culture since anti-IL-4 neutralizing antibody completely abrogated the priming of IL-4-secreting cells, Anti-B7-2 but not anti-B7-1 inhibited the ability of IL-10-DC to prime T cells to secrete IL-4. Furthermore, the ability of IL-10 DC to prime for IL-4-secreting T cells was closely related to the down-regulation of CD40 ligand-mediated IL-12 p70 production by DC in the primary cultures and was markedly reduced by adding exogenous IL-12 to the priming cultures. Thus, our findings indicate that early immunologic events that drive T(h)2 differentiation involve the effects of IL-10 on DC.