Salazar-Onfray F, Petersson M, Franksson L, Matsuda M, Blankenstein T, Kärre K, Kiessling R
Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
J Immunol. 1995 Jun 15;154(12):6291-8.
IL-10 has a variety of effects including: inhibition of monocyte MHC class II-dependent Ag presentation, Th1 cytokine production, and inhibition of T cell proliferation. Recently we have shown that IL-10 inhibits Ag presentation to human tumor-specific and allospecific CTL. In the present study we showed that transfection of the mouse lymphoma RMA (H-2b) with the IL-10 gene induced conversion to a RMA-S-like phenotype. The changes included an inhibition of lysis by minor histocompatibility or tumor Ag-specific CTLs and, conversely, a dramatic increase in susceptibility to lysis by NK cells. The RMA-10 transfectants showed levels of H-2 expression as low or even lower than those found on RMA-S. The levels of tested adhesion molecules were unaltered. Treatment of RMA with rIL-10 gave a less pronounced change in phenotype. In addition, relative to untreated target cells, IL-10 pretreated cells or IL-10 transfectants were unaltered in their capacity to affect cytotoxicity by cold target inhibition, arguing against the possibility that the observed effect could be a direct effect of IL-10 on the CTL. The expression of H-2 was partially restored by coculturing RMA-10 transfectants with class I-binding peptides. Taken together, these results indicate that IL-10 exerts a post-transcriptional effect on H-2 expression, compatible with an induced decrease in the access of peptides to the MHC class I complex. IL-10 is the first cytokine reported to have this effect and also the first factor shown to induce NK sensitivity and reduced sensitivity to CTL, an effect that may be of physiologic relevance.
白细胞介素-10具有多种作用，包括：抑制单核细胞MHC II类分子依赖性抗原呈递、Th1细胞因子产生以及抑制T细胞增殖。最近我们发现白细胞介素-10可抑制抗原呈递给人肿瘤特异性和同种异体特异性细胞毒性T淋巴细胞（CTL）。在本研究中，我们发现用白细胞介素-10基因转染小鼠淋巴瘤RMA（H-2b）可诱导其转变为类似RMA-S的表型。这些变化包括抑制次要组织相容性或肿瘤抗原特异性CTL的裂解作用，相反，对NK细胞裂解的敏感性显著增加。RMA-10转染子的H-2表达水平与RMA-S上的水平一样低甚至更低。所检测的黏附分子水平未改变。用重组白细胞介素-10处理RMA后，表型变化不明显。此外，相对于未处理的靶细胞，经白细胞介素-10预处理的细胞或白细胞介素-10转染子通过冷靶抑制影响细胞毒性的能力未改变，这排除了所观察到的效应可能是白细胞介素-10对CTL的直接作用的可能性。通过将RMA-10转染子与I类结合肽共培养，H-2的表达部分得以恢复。综上所述，这些结果表明白细胞介素-10对H-2表达发挥转录后效应，这与诱导肽进入MHC I类复合物的途径减少相一致。白细胞介素-10是首个被报道具有这种效应的细胞因子，也是首个被证明可诱导NK敏感性增加和对CTL敏感性降低的因子，这种效应可能具有生理相关性。
