Influence of CD4 T cells and the source of major histocompatibility complex class II‐restricted peptides on cytotoxic T‐cell priming by dendritic cells-猫眼课题宝

CD4 T 细胞和主要组织相容性复合物 II 类限制性肽的来源对树突状细胞启动细胞毒性 T 细胞的影响

DOI：

10.1046/j.0019-2805.2001.01343.x

发表时间：

2002

期刊：

Immunology

影响因子：

6.4

通讯作者：

中科院分区：

医学2区

文献类型：

作者：

B. Faiola;C. Doyle;E. Gilboa;S. Nair

我们之前已经报道，在体内，主要组织相容性复合体(MHC)I类限制性多肽冲击的骨髓来源的树突状细胞(DC)可以有效地启动细胞毒性T淋巴细胞(CTL)反应。在此，我们通过在体外和体内检测II类缺陷(C2d)DC、II类突变(Αβ突变)DC和自体血清产生的DC(AS DC)递呈I类限制性抗原的能力，来评估CD4+T细胞在DC诱导CD8+CTL中的作用。从II类基因敲除小鼠和表达突变II类但不能结合CD4的转基因小鼠的骨髓中产生的DC的表型与野生型(Wt)DC相似，只是在MHC II类表达方面。C2d和ΑβMUT DC在体外完全能够向T细胞杂交瘤呈递I类限制性卵清蛋白(OVA)多肽，但在体内不能激发CTL反应。C2d DC上II类表达的恢复允许启动CTL反应；因此，CTL启动的缺陷确实是由于缺乏II类表达所致。同样，在自体血清中产生的DC不能启动CTL反应，因为这些DC只表达‘自身’II类表位，因此不会激活同基因的CD4+T细胞。外源性II类表位的加入挽救了AS DC启动CTL反应的能力。这些观察结果提供了令人信服的证据，表明DC在体内有效地诱导CTL需要同时呈递用于CD4+T细胞诱导的II类表位。

We have previously reported that bone marrow derived dendritic cells (DC) pulsed with major histocompatibility complex (MHC) class I‐restricted peptide efficiently prime a cytotoxic T lymphocyte (CTL) response in vivo. Here we assess the involvement of CD4+ T cells in the induction of CD8+ CTL by DC by testing the ability of class II‐deficient (C2D) DC, class II mutant (Αβmut) DC and autologous serum generated DC (AS DC) to present class I‐restricted antigens in vitro and in vivo. DC generated from the bone marrow of class II knockout mice and transgenic mice expressing a mutant class II that can not bind CD4 were phenotypically similar to wild type (wt) DC, except with regard to MHC class II expression. The C2D and Αβmut DC, though fully capable of presenting the class I‐restricted ovalbumin (OVA) peptide to a T‐cell hybridoma in vitro, failed to prime a CTL response in vivo. Restoration of class II expression on C2D DC allowed priming of a CTL response; thus, the defect in CTL priming was indeed caused by the absence of class II expression. Likewise, DC generated in autologous serum were unable to prime a CTL response as these DC only express ‘self’ class II epitopes and therefore would not activate syngeneic CD4+ T cells. Addition of exogenous class II epitopes rescued the ability of AS DC to prime a CTL response. These observations provide convincing evidence that efficient CTL induction by DC in vivo requires concomitant presentation of class II epitopes for CD4+ T‐cell induction.

Disruption of the CD4-major histocompatibility complex class II interaction blocks the development of CD4(+) T cells in vivo.