Alleva D G, Burger C J, Elgert K D
Department of Biology, Virginia Polytechnic Institute, Blacksburg 24061-0406.
Oncol Res. 1994;6(4-5):219-28.
Tumor growth causes macrophages (M phi) to suppress T-cell proliferation by inducing M phi production of soluble suppressor molecules. Because interleukin (IL)-10 inhibits production of most M phi-derived molecules, we investigated the effects of IL-10 on murine M phi suppressor function during tumor growth. When acting as accessory cells during alloantigen-induced CD4+ T-cell proliferation, syngeneic tumor-bearing host (TBH) peritoneal M phi suppressed normal host (NH) T-cell proliferation more than their normal counterparts. Exogenous IL-10 suppressed alloantigen-stimulated CD4+ T-cell proliferation in the absence of accessory M phi, but it blocked TBH M phi-mediated suppression. IL-10 pretreatment of M phi reversed suppression mediated by TBH M phi but did not affect NH M phi activity. Supernatant transfer experiments showed that IL-10 blocked TBH M phi-mediated suppression by inhibiting soluble suppressor molecule production. Activated TBH M phi produced greater quantities of the suppressor molecules tumor necrosis factor-alpha, nitric oxide, prostaglandin E2, and granulocyte-macrophage colony-stimulating factor than NH M phi did. Exogenous IL-10 reduced production of these molecules by TBH M phi more than by NH M phi. Activated TBH M phi produced more IL-10 than NH M phi, suggesting that endogenous IL-10 contributes to increased TBH M phi sensitivity to exogenous IL-10's inhibitory action. The antibody-mediated neutralization of endogenous IL-10 activity relieved NH, but not TBH, M phi-mediated suppression of T-cell proliferation. This result supports the idea that TBH M phi are more sensitive to the inhibitory action of IL-10 on suppressor molecule production. IL-10 is known to inhibit M phi antigen-presenting cell-dependent helper T-cell proliferation. We report here that IL-10 restores TBH helper T-cell functions by blocking accessory M phi production of inhibitory molecules. This restoration suggests that IL-10's M phi deactivating activity provides an upregulatory role in immunocompromised individuals where suppressor M phi are abundant.
肿瘤生长会导致巨噬细胞（M phi）通过诱导M phi产生可溶性抑制分子来抑制T细胞增殖。由于白细胞介素（IL）-10可抑制大多数源自M phi的分子的产生，我们研究了IL-10在肿瘤生长过程中对小鼠M phi抑制功能的影响。当在同种异体抗原诱导的CD4 + T细胞增殖过程中作为辅助细胞时，同基因荷瘤宿主（TBH）腹膜M phi比正常宿主（NH）的对应M phi更能抑制正常宿主（NH）T细胞增殖。在没有辅助M phi的情况下，外源性IL-10可抑制同种异体抗原刺激的CD4 + T细胞增殖，但它可阻断TBH M phi介导的抑制作用。对M phi进行IL-10预处理可逆转TBH M phi介导的抑制作用，但不影响NH M phi的活性。上清液转移实验表明，IL-10通过抑制可溶性抑制分子的产生来阻断TBH M phi介导的抑制作用。与NH M phi相比，活化的TBH M phi产生的抑制分子肿瘤坏死因子-α、一氧化氮、前列腺素E2和粒细胞-巨噬细胞集落刺激因子的量更多。外源性IL-10使TBH M phi产生的这些分子的量减少得比NH M phi更多。活化的TBH M phi产生的IL-10比NH M phi更多，这表明内源性IL-10有助于提高TBH M phi对外源性IL-10抑制作用的敏感性。抗体介导的内源性IL-10活性的中和作用减轻了NH M phi介导的T细胞增殖抑制作用，但未减轻TBH M phi介导的抑制作用。这一结果支持了TBH M phi对IL-10对抑制分子产生的抑制作用更敏感这一观点。已知IL-10可抑制M phi抗原呈递细胞依赖性辅助性T细胞增殖。我们在此报告，IL-10通过阻断辅助性M phi产生抑制性分子来恢复TBH辅助性T细胞功能。这种恢复表明，IL-10的M phi失活活性在抑制性M phi丰富的免疫受损个体中发挥上调作用。
