Larregina A T, Morelli A E, Kolkowski E, Sanjuan N, Barboza M E, Fainboim L
Department of Microbiology, School of Medicine, University of Buenos Aires, Argentina.
Immunology. 1997 Jun;91(2):303-13. doi: 10.1046/j.1365-2567.1997.00250.x.
Different reasons account for the lack of information about the expression of cytokine receptors on human dendritic cells (DC): (a) DC are a trace population; (b) the proteolytic treatment used to isolate DC may alter enzyme-sensitive epitopes; and (c) low numbers of receptors per cell. In the present work the expression of cytokine receptors was analysed by flow cytometry on the population of dermal DC (DDC) that spontaneously migrate from short-term culture dermal explants. DDC obtained after dermal culture were CD1alow, CD1b+, CD1c+, human leucocyte antigen (HLA)-DR+, CD11chigh, CD11b+ and CD32+. The DC lineage was confirmed by ultrastructural analysis. DDC expressed interleukin (IL)-1R type 1 (monoclonal antibody (mAb) hIL-1R1-M1; and 6B5); IL-1R type 2 (mAb hIL-1R2-M22); IL-2R alpha chain (mAb anti-Tac; and hIL-2R-M1) and IL-2R gamma chain (mAb 3B5; and AG14C). DDC did not stain for IL-2R beta chain using four mAbs recognizing two different epitopes of IL-2R beta (mAb 2R-B; Mik-beta 1; and CF1; Mik-beta 3, respectively). DDC were also positive for the cytokine binding chains (alpha chains) of IL-3R (mAb 9F5); IL-4R (mAb hIL-4R-M57; and S456C9); and IL-7R (mAb hIL-7R-M20; and R3434). DDC showed low levels of IL-6R alpha chain (mAb B-F19; B-R6; and B-E23) and its signal transducer gp130 (mAb A2; and B1). DDC strongly expressed interferon-gamma receptor (IFN-gamma R) (mAb GIR-208) and were negative for IL-8R (mAb B-G20; and B-F25). All DDC were highly positive for granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) alpha chain (mAb hGM-CSFR-M1; SC06; SC04, and 8G6) and to a lesser extent for the common beta chain of GM-CSFR, IL-3R and IL-5R (mAb 3D7). On the other hand, reactivity was not found for granulocyte colony-stimulating factor receptor (G-CSFR) (mAb hGCSFR-M1) nor macrophage colony-stimulating factor receptor (M-CSFR) (mAb 7-7A3-17) confirming the DC lineage of DDC. As previously reported for lymphoid DC, DDC expressed tumour necrosis factor receptort (TNFR) 75000 MW (mAb utr-1; hTNFR-M1; and MR2-1) but lacked TNFR 55000 MW (mAb htr-9; MR1-1; and MR1-2). In summary, DDC express receptors for a broad panel of cytokines, even receptors for cytokines whose effects on DC are still unknown (i.e. IL-2R alpha gamma; IL-6R alpha/gp 130; IL-7R alpha gamma).
关于人类树突状细胞(DC)上细胞因子受体表达信息匮乏的原因有多种:(a)DC是一个微量群体;(b)用于分离DC的蛋白水解处理可能会改变酶敏感表位;(c)每个细胞上的受体数量较少。在本研究中,通过流式细胞术分析了从短期培养的皮肤外植体中自发迁移的真皮DC(DDC)群体上细胞因子受体的表达。皮肤培养后获得的DDC为CD1a低、CD1b +、CD1c +、人类白细胞抗原(HLA)-DR +、CD11c高、CD11b +和CD32 +。通过超微结构分析证实了DC谱系。DDC表达白细胞介素(IL)-1Ⅰ型受体(单克隆抗体(mAb)hIL-1R1-M1;和6B5);IL-1Ⅱ型受体(mAb hIL-1R2-M22);IL-2Rα链(mAb抗Tac;和hIL-2R-M1)和IL-2Rγ链(mAb 3B5;和AG14C)。使用识别IL-2Rβ两个不同表位的四种mAb(分别为mAb 2R-B;Mik-β1;和CF1;Mik-β3),DDC未被IL-2Rβ链染色。DDC对IL-3R(mAb 9F5)、IL-4R(mAb hIL-4R-M57;和S456C9)和IL-7R(mAb hIL-7R-M20;和R3434)的细胞因子结合链(α链)也呈阳性。DDC显示IL-6Rα链(mAb B-F19;B-R6;和B-E23)及其信号转导子gp130(mAb A2;和B1)水平较低。DDC强烈表达干扰素-γ受体(IFN-γR)(mAb GIR-208),对IL-8R呈阴性(mAb B-G20;和B-F25)。所有DDC对粒细胞-巨噬细胞集落刺激因子受体(GM-CSFR)α链(mAb hGM-CSFR-M1;SC06;SC04,和8G6)均呈高度阳性,对GM-CSFR、IL-3R和IL-5R的共同β链(mAb 3D7)呈弱阳性。另一方面,未发现粒细胞集落刺激因子受体(G-CSFR)(mAb hGCSFR-M1)和巨噬细胞集落刺激因子受体(M-CSFR)(mAb 7-7A3-17)的反应性,这证实了DDC的DC谱系。如先前对淋巴样DC的报道,DDC表达肿瘤坏死因子受体(TNFR)75000 MW(mAb utr-1;hTNFR-M1;和MR2-1),但缺乏55000 MW的TNFR(mAb htr-9;MR1-1;和MR1-2)。总之,DDC表达多种细胞因子的受体,甚至包括对DC作用尚不清楚的细胞因子的受体(即IL-2Rαγ;IL-6Rα/gp 130;IL-7Rαγ)。