IL-10 inhibits tumor antigen presentation by epidermal antigen-presenting cells.
IL-10 inhibits tumor antigen presentation by epidermal antigen-presenting cells.
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DOI：
10.4049/jimmunol.154.3.1280
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发表时间：
1995-02
影响因子：
4.4
通讯作者：
S. Beissert;J. Hosoi;S. Grabbe;A. Asahina;R. Granstein
中科院分区：
文献类型：
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作者：
S. Beissert;J. Hosoi;S. Grabbe;A. Asahina;R. Granstein
IL-10抑制朗格汉斯细胞(LC)抗原提呈给Th1克隆。由于LC能够呈递肿瘤相关抗原(TAA)，用于原发和继发性肿瘤免疫反应，我们在S1509a梭形细胞瘤(H-2a)免疫模型中观察了IL-10对LC抗原呈递的影响。由于对S1509a的免疫诱导需要LC暴露于粒细胞-巨噬细胞(GM)-CSF，该系统也使我们能够研究GM-CSF和IL-10对LC的调节作用。经GM-CSF暴露和TAA冲击的表皮细胞(EC)对接种的肿瘤细胞的生长抑制作用，可使未接种的CAF1(H-2a/d)小鼠免疫抗S1509a。在GM-CSF暴露前将EC与IL-10孵育可完全抑制该系统中的Ag提呈。值得注意的是，无论是将EC与IL-10和GM-CSF共孵育(不加IL-10预孵育)，还是在GM-CSF孵育后再用IL-10处理，都不能起到下调作用。IL-10调节EC递呈TAA的能力也被检测为二次免疫反应。在体外用TAA冲击EC，然后将其注射到肿瘤免疫小鼠的后脚垫中，24小时肿胀被评估为迟发型超敏反应的衡量标准。在TAA暴露前预先孵育IL-10可显著抑制在随后或随后暴露于GM-CSF的情况下迟发性超敏反应的诱发。将EC与IL-10和GM-CSF共同孵育，或在GM-CSF后暴露于IL-10，均可导致正常反应。提示IL-10可能是肿瘤免疫应答中LC抗原提呈功能的重要调节因子。当IL-10在暴露于GM-CSF之前进行治疗时，IL-10似乎可以特异性地阻止GM-CSF诱导的LC抗原提呈功能的成熟，但不能逆转已建立的成熟状态。
IL-10 inhibits Langerhans cell (LC) Ag presentation to Th1 clones. As LC are capable of presenting tumor-associated Ags (TAA) for primary and secondary tumor immune responses, we examined the effect of IL-10 on LC Ag presentation in a model of immunity to the S1509a spindle cell tumor (H-2a). Because induction of immunity to S1509a requires exposure of LC to granulocyte-macrophage (GM)-CSF, this system also allowed us to study the regulatory interactions of GM-CSF and IL-10 on LC. Naive CAF1 (H-2a/d) mice could be immunized against S1509a by injection with GM-CSF-exposed and TAA-pulsed epidermal cells (EC) as assessed by inhibition of the growth of inoculated tumor cells. Incubation of EC in IL-10 before GM-CSF exposure completely inhibited Ag presentation in this system. Significantly, neither co-incubation of EC in IL-10 and GM-CSF (without preincubation in IL-10) nor IL-10 treatment after GM-CSF incubation was able to exert a down-regulatory effect. The ability of IL-10 to modulate EC presentation of TAA for a secondary immune response was also examined. EC were pulsed with TAA in vitro and then injected into a hind footpad of tumor-immune mice with 24 h swelling assessed as a measure of delayed-type hypersensitivity. Preincubation in IL-10 before TAA exposure significantly inhibited elicitation of delayed-type hypersensitivity with or without subsequent exposure to GM-CSF. Co-incubation of EC in IL-10 and GM-CSF or exposure to IL-10 after GM-CSF led to a normal response. These data indicate that IL-10 may serve as an important regulator of LC Ag-presenting function for tumor immune responses. IL-10 appears to specifically prevent the GM-CSF-induced maturation of LC Ag-presenting function when treatment with IL-10 occurs before exposure to GM-CSF but does not reverse the established mature state.