Regulation of CD40 ligand expression on naive CD4 T cells: A role for TCR but not co-stimulatory signals
Regulation of CD40 ligand expression on naive CD4 T cells: A role for TCR but not co-stimulatory signals
复制标题
DOI：
10.1093/intimm/8.2.275
复制
发表时间：
1996-02-01
影响因子：
4.4
通讯作者：
Croft, M
中科院分区：
文献类型：
--
作者：
Jaiswal, AI;Dubey, C;Croft, M
我们研究了TCR和辅助共刺激信号在诱导CD 4细胞上的CD 40配体（CD 40 L）中的作用。使用来自TCR转基因小鼠的幼稚T细胞，特异性针对鸽子细胞色素c的肽，我们表明，与IL-2分泌相反，CD 40 L表达主要由通过TCR的信号传导调节，由辅助分子相互作用增强，但共刺激信号几乎不起作用。表达ICAM-1、B7-1或两种分子的II类MHC（+）成纤维细胞抗原呈递细胞（APC）在幼稚T细胞上以高水平诱导CD 40 L，在5 h达到峰值，而不表达任何辅助分子的成纤维细胞仅诱导低水平。表达的强度和持续时间的差异被视为刺激后与ICAM-和B7-表达APC，与ICAM的存在导致更大和更长的表达，虽然这两种分子一起是最有效的。在粘附相互作用对TCR信号传导没有影响的系统中研究了从辅助分子递送的共刺激信号的参与。使用抗-CD 3或缺乏辅助分子的抗原脉冲APC提供TCR信号，共刺激来自不呈递抗原的表达抗-CD 28或辅助分子的成纤维细胞。在没有共刺激物的情况下，抗CD 3诱导高CD 40 L表达，但没有IL-2产生，并且提供共刺激信号，尽管诱导大量IL-2，但没有增加CD 40 L表达。此外，低CD 40 L的表达诱导的抗原在辅助分子的情况下，并没有增强共刺激，虽然IL-2强烈上调。这些研究表明，CD 40 L在初始CD 4细胞上的有效表达确实需要APC上的辅助分子。然而，与IL-2分泌相反，这些分子对CD 40 L诱导的作用不是共刺激，而是粘附，推测允许通过TCR产生更强或更长时间的信号。使用树突状细胞作为APC证实了ICAM和B7在幼稚CD 4活化期间的协同作用，当使用CTLA-4-Ig和抗LFA-1两者来阻断这些分子时，观察到CD 40 L表达以及IL-2分泌的几乎完全抑制。
We have investigated the roles of TCR and accessory co-stimulatory signals in the induction of CD40 ligand (CD40L) on CD4 cells. Using naive T cells from TCR transgenic mice, specific for a peptide of pigeon cytochrome c, we show that in contrast to IL-2 secretion, CD40L expression is regulated primarily by signaling through the TCR, is enhanced by accessory molecule interactions, but co-stimulatory signals play little if any role. CD40L was induced at high levels on naive T cells, peaking at 5 h, by class II MHC(+) fibroblast antigen-presenting cells (APC) which expressed either ICAM-1, B7-1 or both molecules, whereas only low levels were induced by fibroblasts which did not express any accessory molecules. Differences in intensity and duration of expression were seen following stimulation with ICAM- and B7-expressing APC, with the presence of ICAM resulting in greater and longer expression, although both molecules together were most efficient. The involvement of co-stimulatory signals delivered from accessory molecules was investigated in systems where there was no effect on TCR signaling from adhesive interactions. Anti-CD3, or antigen-pulsed APC lacking accessory molecules, were used to provide the TCR signal, with co-stimulus from either anti-CD28 or accessory molecule-expressing fibroblasts not presenting antigen. Anti-CD3 in the absence of co-stimuli induced high CD40L expression but no IL-2 production and provision of co-stimulatory signals, although inducing large quantities of IL-2, did not increase CD40L expression. In addition, low CD40L expression induced by antigen presented in the absence of accessory molecules was not enhanced by co-stimulation, although IL-2 was strongly up-regulated. These studies suggest that efficient expression of CD40L on naive CD4 cells does require accessory molecules on APC. However, the role of these molecules for CD40L induction, as opposed to IL-2 secretion, is not one of co-stimulation but one of adhesion, presumably allowing stronger or more prolonged signals to be generated through the TCR. The synergistic role of ICAM and B7 during naive CD4 activation was confirmed using dendritic cells as APC, with nearly complete inhibition of CD40L expression as well as IL-2 secretion being seen when both CTLA-4-lg and anti-LFA-1 were used to block these molecules.