COSTIMULATORY SIGNALS MODULATE THE ANTIPROLIFERATIVE EFFECTS OF AGENTS THAT ELEVATE CAMP IN T-CELLS
COSTIMULATORY SIGNALS MODULATE THE ANTIPROLIFERATIVE EFFECTS OF AGENTS THAT ELEVATE CAMP IN T-CELLS
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DOI：
10.1006/cimm.1994.1261
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发表时间：
1994-10-01
影响因子：
4.3
通讯作者：
ROSZMAN, TL
中科院分区：
文献类型：
--
作者：
BARTIK, MM;BAUMAN, GP;ROSZMAN, TL
在cAMP诱导剂的存在下，用固定化抗CD 3单克隆抗体（mAb）刺激高度纯化的人T细胞导致这些T细胞增殖的抑制。在本研究中，进行了实验，以确定共刺激信号如何调节cAMP升高剂对抗CD 3单抗刺激的T细胞增殖和白细胞介素2（IL-2）分泌的抑制作用。因此，在存在或不存在辅助细胞、抗CD 28 mAb或佛波醇肉豆蔻酸（PMA）的情况下，在存在腺苷酸环化酶（AC）连接的受体激动剂前列腺素E（2）（PGE（2））或异丙肾上腺素（ISO）以及AC激活剂毛喉素（FSK）或cAMP类似物二丁酰-cAMP（dB-cAMP）的情况下，测定抗CD 3 mAb诱导的T细胞增殖水平。虽然所有三种共刺激因子增强抗CD 3 mAb诱导的T细胞增殖和IL-2分泌的水平，但它们克服cAMP升高剂的免疫抑制作用的能力是可变的。共刺激信号逆转cAMP升高剂对抗CD 3单抗诱导的T细胞增殖和IL-2分泌的抑制作用的效力顺序为PMA >辅助细胞>抗CD 28单抗。注意到共刺激信号克服各种cAMP诱导剂的免疫抑制作用的能力的差异。因此，PGE（2）或ISO对T细胞增殖或IL-2分泌的作用比FSK或dB-cAMP引起的作用更容易被共刺激信号克服。旨在研究这些作用机制的实验表明，无论是辅助细胞还是抗CD 28 mAb都不能改变cAMP升高剂刺激的T细胞中cAMP积累或蛋白激酶A（PKA）活性的水平。然而，PMA被发现减少cAMP的积累和PKA活性在T细胞刺激PGE（2）或ISO，但不FSK。这些结果表明，当抗原特异性T细胞与抗原呈递细胞相互作用时，天然存在的物质如PGE（2）或儿茶酚胺的整体免疫抑制作用可能会被共刺激信号改变。(C)1994年出版社出版。
Stimulation of highly purified human T cells with immobilized anti-CD3 monoclonal antibody (mAb) in the presence of cAMP-inducing agents results in inhibition of proliferation by these T cells. In the present study, experiments were performed to determine how costimulatory signals modulate the inhibitory effects of cAMP-elevating agents on proliferation and interleukin 2 (IL-2) secretion by anti-CD3 mAb-stimulated T cells. Accordingly, the level of anti-CD3 mAb-induced T cell proliferation was determined in the presence or absence of accessory cells, anti-CD28 mAb, or phorbol myristic acid (PMA) in the presence of the adenylyl cyclase (AC)-linked receptor agonists prostaglandin E(2) (PGE(2)), or isoproterenol (ISO) as well as the AC activator forskolin (FSK) or the cAMP analog dibutyryl-cAMP (dB-cAMP). While all three costimulators enhanced the level of anti-CD3 mAb-induced T cell proliferation and IL-2 secretion, they were variable in their ability to overcome the immunosuppressive effects of the cAMP elevating agents. The order of potency of the costimulatory signals in reversing the inhibitory effects of cAMP-elevating agents on anti-CD3 mAb-induced T cell proliferation and IL-2 secretion was PMA > accessory cells > anti-CD28 mAb. Differences were noted in the ability of the costimulatory signals to overcome the immunosuppressive effects of the various cAMP-inducing agents. Thus, the effects of PGE(2) or ISO on T cell proliferation or IL-2 secretion were more readily overcome by costimulatory signals than those elicited by FSK or dB-cAMP. Experiments designed to investigate the mechanisms involved in these effects showed that neither accessory cells nor anti-CD28 mAb altered the level of cAMP accumulation or protein kinase A (PKA) activity in T cells stimulated with cAMP-elevating agents. However, PMA was found to decrease both cAMP accumulation and PKA activity in T cells stimulated with PGE(2) or ISO but not FSK. These results suggest that the overall immunosuppressive effects of naturally occurring substances such as PGE(2) or catecholamines may be altered by costimulatory signals when antigen-specific T cells interact with antigen-presenting cells. (C) 1994 Academic Press, Inc.