Beissert S, Hosoi J, Grabbe S, Asahina A, Granstein R D
Massachusetts General Hospital/Harvard Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital-East and Harvard Medical School, Charlestown 02129.
J Immunol. 1995 Feb 1;154(3):1280-6.
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.
白细胞介素-10（IL-10）抑制朗格汉斯细胞（LC）向Th1克隆呈递抗原。由于LC能够呈递肿瘤相关抗原（TAA）以引发原发性和继发性肿瘤免疫反应，我们在对S1509a梭形细胞瘤（H-2a）的免疫模型中研究了IL-10对LC抗原呈递的影响。因为对S1509a的免疫诱导需要LC暴露于粒细胞-巨噬细胞（GM）-集落刺激因子（CSF），该系统还使我们能够研究GM-CSF和IL-10对LC的调节相互作用。通过接种肿瘤细胞生长的抑制评估，未接触过抗原的CAF1（H-2a/d）小鼠可通过注射经GM-CSF处理且负载TAA的表皮细胞（EC）来免疫S1509a。在GM-CSF处理之前将EC在IL-10中孵育完全抑制了该系统中的抗原呈递。重要的是，无论是将EC在IL-10和GM-CSF中共同孵育（未预先在IL-10中孵育）还是在GM-CSF孵育后进行IL-10处理，均无法发挥下调作用。我们还研究了IL-10调节EC对TAA的呈递以引发继发性免疫反应的能力。将EC在体外负载TAA，然后注射到肿瘤免疫小鼠的后足垫中，以24小时后的肿胀作为迟发型超敏反应的指标进行评估。在TAA暴露之前在IL-10中预先孵育显著抑制了迟发型超敏反应的激发，无论随后是否暴露于GM-CSF。将EC在IL-10和GM-CSF中共同孵育或在GM-CSF后暴露于IL-10导致正常反应。这些数据表明，IL-10可能是肿瘤免疫反应中LC抗原呈递功能的重要调节因子。当在暴露于GM-CSF之前用IL-10进行处理时，IL-10似乎特异性地阻止了GM-CSF诱导的LC抗原呈递功能的成熟，但不会逆转已建立的成熟状态。
