Hong Li, Webb Tonya J, Wilkes David S
Center for Immunobiology, Indiana University School of Medicine, Indianapolis, IN 46202-5120, USA.
Immunol Lett. 2007 Feb 15;108(2):174-8. doi: 10.1016/j.imlet.2006.12.003. Epub 2007 Jan 8.
Expression of the CD8 alpha alpha homodimer has been used to differentiate lymphoid (CD8alpha(+)) from myeloid (CD8alpha(-)) dendritic cells (DCs). We have reported that CD8alpha(+) and CD8alpha(-) DCs have differential abilities to stimulate proliferation in allogeneic T cells. However, no specific function has been attributed to DC-derived CD8alpha. The current study examines the hypothesis that CD8 alpha alpha expression on DCs regulates DC-induced T cell activation. CD8alpha(-) transduced bone marrow-derived DCs were more potent stimulators of T cell proliferation, and produced significantly greater quantities of IL-12 in co-culture with T cells. LCK, a kinase whose expression is reported to be T cell-restricted and known to bind to the cytoplasmic tail of CD8 alpha beta in T cells, was detected readily in primary CD8alpha(+) splenic DCs and at greater levels than CD8alpha(-) DCs from the same tissues. LCK also co-precipitated with CD8alpha on immunblots strongly suggesting its role in CD8alpha(+) DC-induced T cell activation. Collectively, these data show that CD8alpha expressed on DC may not only be a lineage/maturation marker but also contribute to DC function.
CD8αα同型二聚体的表达已被用于区分淋巴样(CD8α(+))和髓样(CD8α(-))树突状细胞(DC)。我们曾报道,CD8α(+)和CD8α(-) DC在刺激同种异体T细胞增殖方面具有不同能力。然而,DC衍生的CD8α尚未被赋予特定功能。当前研究检验了DC上CD8αα表达调节DC诱导的T细胞活化这一假说。转导了CD8α(-)的骨髓来源DC是更强的T细胞增殖刺激剂,并且在与T细胞共培养时产生的IL-12量显著更多。LCK是一种激酶,据报道其表达受T细胞限制,并且已知在T细胞中与CD8αβ的胞质尾部结合,在原代CD8α(+)脾DC中很容易检测到,且水平高于来自相同组织的CD8α(-) DC。在免疫印迹中,LCK也与CD8α共沉淀,强烈表明其在CD8α(+) DC诱导的T细胞活化中的作用。总体而言,这些数据表明DC上表达的CD8α不仅可能是谱系/成熟标志物,还对DC功能有贡献。