Taieb Aurele, Breitinger Jeremy J, Unadkat Jignesh V, Shufesky William J, Morelli Adrian E, Thomson Angus W, Lee W P Andrew, Feili-Hariri Maryam
Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Clin Immunol. 2007 May;123(2):176-89. doi: 10.1016/j.clim.2006.12.007. Epub 2007 Feb 5.
The influence of GM+IL-4 and Flt3 ligand (FL) on phenotype and function of BM-derived DC from Lewis rats was investigated. GM+IL-4-induced DC, despite expression of CD80/CD86, were less stimulatory than FL-induced DC that expressed low CD80/CD86 and were efficient stimulators of allogeneic T cells. GM+IL-4 DC were CD11b+ OX62lo, whereas FL DC were CD11blo OX62+. Following activation, GM+IL-4 DC produced IL-10 and IL-6, but no IL-12p70, and were resistant to further maturation. FL DC produced IL-12p70, IFN-alpha/beta, IL-10 and IL-6 and underwent maturation. Repeated stimulation of T cells with GM+IL-4 DC inhibited proliferation, cytokine production and induced early T cell apoptosis. FL DC-activated T cells produced large amounts of IFN-gamma/IL-10 and exhibited late T cell apoptosis/necrosis. In vivo, GM+IL-4 DC induced alloAg-specific hyporesponsiveness following T cell restimulation. These results demonstrate that GM+IL-4 DC display intrinsic regulatory properties, inducing passive-cell-death in T cells with potential for inactivation/regulation of alloreactive T cells in transplantation.
研究了GM + IL-4和Flt3配体（FL）对Lewis大鼠骨髓来源树突状细胞（DC）表型和功能的影响。GM + IL-4诱导的DC尽管表达CD80/CD86，但刺激作用比FL诱导的DC弱，FL诱导的DC CD80/CD86表达低，是同种异体T细胞的有效刺激剂。GM + IL-4 DC为CD11b + OX62lo，而FL DC为CD11blo OX62 +。激活后，GM + IL-4 DC产生IL-10和IL-6，但不产生IL-12p70，并且对进一步成熟具有抗性。FL DC产生IL-12p70、IFN-α/β、IL-10和IL-6并经历成熟。用GM + IL-4 DC重复刺激T细胞会抑制增殖、细胞因子产生并诱导早期T细胞凋亡。FL DC激活的T细胞产生大量IFN-γ/IL-10并表现出晚期T细胞凋亡/坏死。在体内，GM + IL-4 DC在T细胞再刺激后诱导同种抗原特异性低反应性。这些结果表明，GM + IL-4 DC具有内在调节特性，可诱导T细胞发生被动细胞死亡，有可能使移植中的同种反应性T细胞失活/调节。
