Department of Pathology, Stanford University School of Medicine (Blood Center), Palo Alto, California, United States of America.
PLoS One. 2013 Oct 2;8(10):e76258. doi: 10.1371/journal.pone.0076258. eCollection 2013.
Two critical functions of dendritic cells (DC) are to activate and functionally polarize T cells. Activated T cells can, in turn, influence DC maturation, although their effect on de novo DC development is poorly understood. Here we report that activation of T cells in mice, with either an anti-CD3 antibody or super antigen, drives the rapid formation of CD209(+)CD11b(+)CD11c(+) MHC II(+) DC from monocytic precursors (Mo-DC). GM-CSF is produced by T cells following activation, but surprisingly, it is not required for the formation of CD209(+) Mo-DC. CD40L, however, is critical for the full induction of Mo-DC following T cell activation. T cell induced CD209(+) Mo-DC are comparable to conventional CD209(-) DC in their ability to stimulate T cell proliferation. However, in contrast to conventional CD209(-) DC, CD209(+) Mo-DC fail to effectively polarize T cells, as indicated by a paucity of T cell cytokine production. The inability of CD209(+) Mo-DC to polarize T cells is partly explained by increased expression of PDL-2, since blockade of this molecule restores some polarizing capacity to the Mo-DC. These findings expand the range of signals capable of driving Mo-DC differentiation in vivo beyond exogenous microbial factors to include endogenous factors produced following T cell activation.
树突状细胞 (DC) 的两个关键功能是激活和功能极化 T 细胞。激活的 T 细胞反过来可以影响 DC 的成熟,尽管它们对新生成的 DC 发育的影响知之甚少。在这里,我们报告在小鼠中,T 细胞的激活无论是通过抗 CD3 抗体还是超抗原,都可以从单核细胞前体 (Mo-DC) 中快速形成 CD209(+)CD11b(+)CD11c(+)MHC II(+)DC。GM-CSF 是 T 细胞在激活后产生的,但令人惊讶的是,它不是形成 CD209(+)Mo-DC 所必需的。然而,CD40L 对于 T 细胞激活后 Mo-DC 的完全诱导是至关重要的。T 细胞诱导的 CD209(+)Mo-DC 在刺激 T 细胞增殖的能力上与传统的 CD209(-)DC 相当。然而,与传统的 CD209(-)DC 相反,CD209(+)Mo-DC 不能有效地极化 T 细胞,这表明 T 细胞细胞因子的产生很少。CD209(+)Mo-DC 不能极化 T 细胞的能力部分解释为 PDL-2 的表达增加,因为阻断该分子可以恢复 Mo-DC 的一些极化能力。这些发现扩展了能够在体内驱动 Mo-DC 分化的信号范围,超出了外源性微生物因素,包括 T 细胞激活后产生的内源性因素。