Selective loss of c-Rel compromises dendritic cell activation of T lymphocytes
Selective loss of c-Rel compromises dendritic cell activation of T lymphocytes
复制标题
DOI：
10.1016/s0008-8749(03)00114-x
复制
发表时间：
2003-04-01
影响因子：
4.3
通讯作者：
Liou, HC
中科院分区：
文献类型：
--
作者：
Boffa, DJ;Feng, B;Liou, HC
树突状细胞通过在不同水平的共刺激的背景下呈递抗原来启动免疫应答。树突状细胞的成熟状态决定了随后T细胞应答的数量和质量（Th 1，Th 2）。转录因子的NF-κ B家族的成员先前已经涉及树突状细胞的发育。在这里，我们使用纯合c-Rel缺失的小鼠来研究c-Rel在骨髓来源的树突状细胞功能中的作用。当评估直接呈递时，我们发现c-Rel（-/-）树突状细胞比c-Rel（+/+）树突状细胞诱导更少的同种异体T细胞刺激。此外，当与具有c-Rel（+/+）DC的那些相比时，T细胞与c-Rel（-/-）树突状细胞相遇产生较少的IFN-γ和IL-4。在由c-Rel（-/-）树突状细胞刺激的抗原特异性T细胞中观察到类似程度的功能损害。功能缺陷与经历成熟本身的能力的差异无关，因为LPS暴露在c-Rel（+/+）和cRel（-/-）DC中诱导相似的形态学和细胞表面变化。虽然LPS诱导了NF-κ B家族成员RelB和p65的核活性的代偿性增加，但LPS暴露不能消除与树突状细胞中c-Rel缺失相关的抗增殖T细胞增殖和细胞因子产生的缺陷。综上所述，我们的研究支持c-Rel在树突状细胞共刺激能力中的独特和非冗余作用。(C)2003 Elsevier Science（美国）。All rights reserved.
Dendritic cells initiate the immune response by presenting antigen in the context of varying levels of costimulation. The maturation state of the dendritic cell determines the quantity and quality (Th1, Th2) of the subsequent T cell response. Members of the NF-kappaB family of transcription factors have previously been implicated in dendritic cell development. Here, we used a mouse with a homozygous c-Rel deletion to investigate the role of c-Rel in the function of bone marrow derived dendritic cells. When direct presentation was evaluated, we found c-Rel(-/-) dendritic cells induce less allogeneic T cell stimulation than c-Rel(+/+) dendritic cells. In addition, T cell encounters with c-Rel(-/-) dendritic cells generate less IFN-gamma and IL-4 when compared to those with c-Rel(+/+) DCs. A similar degree of functional compromise was observed in antigen-specific T cells that were stimulated by c-Rel(-/-) dendritic cells. Functional deficits were not linked to differences in the ability to undergo maturation per se, as LPS exposure induced similar morphologic and cell surface changes in both c-Rel(+/+) and cRel(-/-) DCs. Although LPS induced a compensatory increase in the nuclear activity of fellow NF-kappaB family members, RelB and p65, LPS exposure was unable to negate the deficiencies in antologous T cell proliferation and cytokine production associated with the loss of c-Rel in dendritic cells. Taken together, our study supports a unique and non-redundant role for c-Rel in dendritic cell costimulatory capacity. (C) 2003 Elsevier Science (USA). All rights reserved.