DIFFERENTIAL REGULATION OF T-HELPER PHENOTYPE DEVELOPMENT BY INTERLEUKIN-4 AND INTERLEUKIN-10 IN AN ALPHA-BETA-T-CELL-RECEPTOR TRANSGENIC SYSTEM
DIFFERENTIAL REGULATION OF T-HELPER PHENOTYPE DEVELOPMENT BY INTERLEUKIN-4 AND INTERLEUKIN-10 IN AN ALPHA-BETA-T-CELL-RECEPTOR TRANSGENIC SYSTEM
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DOI：
10.1073/pnas.89.13.6065
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发表时间：
1992-07-01
影响因子：
11.1
通讯作者：
MURPHY, KM
中科院分区：
文献类型：
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作者：
HSIEH, CS;HEIMBERGER, AB;MURPHY, KM
为了探究控制辅助性T细胞（Th）表型发育的机制，我们使用了DO10，这是一种转基因小鼠品系，它表达来自卵清蛋白反应性T杂交瘤的α/β - T细胞受体，以此作为初始T细胞的来源，这些初始T细胞可在体外由特定的抗原呈递细胞（APC）呈递的卵清蛋白肽段刺激。我们已经研究了细胞因子和抗原呈递细胞在调节辅助性T细胞表型发育中的作用。白细胞介素4（IL - 4）引导细胞向Th2表型发育，刺激发育中的T细胞产生IL - 4，并抑制IL - 2和干扰素 - γ的产生。当用抗IL - 10抗体中和内源性IL - 10时，脾脏抗原呈递细胞引导细胞向Th1表型发育。介导这些作用的脾脏抗原呈递细胞可能是巨噬细胞或树突状细胞，而非B细胞，因为当B细胞杂交瘤TA3用作抗原呈递细胞时，IL - 10无法影响辅助性T细胞表型的发育。这些结果表明，在免疫应答发生过程中，IL - 4和IL - 10的早期调控以及起始抗原呈递细胞的类型对于决定发育中的T细胞的辅助性T细胞表型至关重要。
To address the mechanisms controlling T helper (T(h)) phenotype development, we used DO10, a transgenic mouse line that expresses the alpha/beta-T-cell receptor from an ovalbumin-reactive T hybridoma, as a source of naive T cells that can be stimulated in vitro with ovalbumin peptide presented by defined antigen-presenting cells (APCs). We have examined the role of cytokines and APCs in the regulation of T(h) phenotype development. Interleukin 4 (IL-4) directs development toward the T(h2) phenotype, stimulating IL-4 and silencing IL-2 and interferon-gamma-production in developing T cells. Splenic APCs direct development toward the T(h1) phenotype when endogenous IL-10 is neutralized with anti-IL-10 antibody. The splenic APCs mediating these effects are probably macrophages or dendritic cells and not B cells, since IL-10 is incapable of affecting T(h) phenotype development when the B-cell hybridoma TA3 is used as the APC. These results suggest that early regulation of IL-4 and IL-10 in a developing immune response and the identity of the initiating APCs are critical in determining the T(h) phenotype of the developing T cells.