Nagata K, Tanaka K, Ogawa K, Kemmotsu K, Imai T, Yoshie O, Abe H, Tada K, Nakamura M, Sugamura K, Takano S
R & D Center, BioMedical Laboratories, Kawagoe, Saitama, Japan.
J Immunol. 1999 Feb 1;162(3):1278-86.
The search for reliable marker molecules discriminating between human Th1 and Th2 cells identified a gene encoding a novel member of the G protein-coupled leukocyte chemoattractant receptor family, which is selectively expressed in Th2 but not Th1 lineage cells, thereby named CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells). Studies with anti-CRTH2 mAbs demonstrated that CRTH2 was expressed in a small population (0.4-6.5%) of CD4+ T cells in fresh PBMCs of healthy adults, but no remarkable expression was seen in B cells and NK cells. In some cases, CD8+ T cells ( approximately 3.5%) expressed CRTH2. Phenotypes of CD4+ T cells expressing CRTH2 were CD45RA-, CD45RO+, and CD25+, similar to those of Ag-activated effector/memory T cells. Freshly isolated CRTH2+ CD4+ T cells produced Th2- but little or no Th1-type cytokines upon stimulation with PMA and ionomycin. In addition, an allergen-induced proliferative response in fresh PBMCs was significantly and selectively reduced by subtracting CRTH2+ cells. Together, these results indicate that CRTH2 is selectively expressed in vivo in an activated state of Th2 cells including allergen-responsive Th2 cells, suggesting its pivotal roles in ongoing Th2-type immune reactions.
对区分人Th1和Th2细胞的可靠标志物分子的研究，鉴定出一个编码G蛋白偶联白细胞趋化因子受体家族新成员的基因，该基因在Th2而非Th1谱系细胞中选择性表达，因此被命名为CRTH2（Th2细胞上表达的趋化因子受体同源分子）。用抗CRTH2单克隆抗体进行的研究表明，CRTH2在健康成年人新鲜外周血单个核细胞（PBMC）中一小部分（0.4 - 6.5%）的CD4⁺T细胞中表达，但在B细胞和NK细胞中未见明显表达。在某些情况下，CD8⁺T细胞（约3.5%）表达CRTH2。表达CRTH2的CD4⁺T细胞的表型为CD45RA⁻、CD45RO⁺和CD25⁺，与抗原激活的效应/记忆T细胞相似。新鲜分离的CRTH2⁺CD4⁺T细胞在用佛波酯（PMA）和离子霉素刺激后产生Th2型细胞因子，但几乎不产生或不产生Th1型细胞因子。此外，通过去除CRTH2⁺细胞，新鲜PBMC中过敏原诱导的增殖反应显著且选择性地降低。这些结果共同表明，CRTH2在包括过敏原反应性Th2细胞在内的Th2细胞的活化状态下在体内选择性表达，提示其在正在进行的Th2型免疫反应中起关键作用。
