Grohmann Ursula, Bianchi Roberta, Orabona Ciriana, Fallarino Francesca, Vacca Carmine, Micheletti Alessandra, Fioretti Maria C, Puccetti Paolo
Department of Experimental Medicine, University of Perugia, 06126 Perugia, Italy.
J Immunol. 2003 Sep 1;171(5):2581-7. doi: 10.4049/jimmunol.171.5.2581.
Murine dendritic cells (DCs) can present Ag in an immunogenic or tolerogenic fashion, the distinction depending on either the occurrence of specialized DC subsets or the maturation or activation state of the DC. Although DC subsets may be programmed to direct either tolerance or immunity, it is not known whether appropriate environmental stimulation can result in complete flexibility of a basic program. Using splenic CD8(-) and CD8(+) DCs that mediate the respective immunogenic and tolerogenic presentation of self peptides, we show that both the in vivo and in vitro activities of either subset can be altered by ligation of specific surface receptors. Otherwise immunogenic CD8(-) DCs become tolerogenic upon B7 ligation by soluble CTLA-4, a maneuver that initiates immunosuppressive tryptophan catabolism. In contrast, CD40 ligation on tolerogenic CD8(+) DCs makes these cells capable of immunogenic presentation. Thus, environmental conditioning by T cell ligands may alter the default function of DC subsets to meet the needs of flexibility and redundancy.
小鼠树突状细胞（DCs）能够以免疫原性或耐受性方式呈递抗原，这种区别取决于特定DC亚群的存在情况或DC的成熟或激活状态。尽管DC亚群可能被编程为引导耐受性或免疫性，但尚不清楚适当的环境刺激是否会导致基本程序的完全灵活性。利用介导自身肽各自免疫原性和耐受性呈递的脾脏CD8(-)和CD8(+) DCs，我们发现任一亚群的体内和体外活性均可通过特定表面受体的连接而改变。原本具有免疫原性的CD8(-) DCs在被可溶性CTLA-4进行B7连接后会变成耐受性，这一操作会启动免疫抑制性色氨酸分解代谢。相反，对耐受性CD8(+) DCs进行CD40连接会使这些细胞具备免疫原性呈递能力。因此，T细胞配体介导的环境调节可能会改变DC亚群的默认功能，以满足灵活性和冗余性的需求。
