DIFFERENTIAL SENSITIVITY OF HUMAN NAIVE AND MEMORY CD4(+) T-CELLS FOR DEXAMETHASONE
DIFFERENTIAL SENSITIVITY OF HUMAN NAIVE AND MEMORY CD4(+) T-CELLS FOR DEXAMETHASONE
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DOI：
10.1093/intimm/7.4.591
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发表时间：
1995-04-01
影响因子：
4.4
通讯作者：
NAGELKERKEN, L
中科院分区：
文献类型：
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作者：
NIJHUIS, EWP;HINLOOPEN, B;NAGELKERKEN, L
比较人CD 45 RA（+）（“幼稚”）和CD 45 RO（+）（“记忆”）CD 4（+）T细胞对地塞米松（DEX）的敏感性。在三种不同的活化途径中，即（i）固定化抗-CDS、（ii）固定化抗-CD 3加可溶性抗-CD 28和（iii）可溶性抗-CDS加可溶性抗-CD 28，初始CD 4（+）T细胞似乎比记忆性CD 4（+）T细胞对DEX更敏感。在抗CD 3系统中，这种灵敏度差异在次优DEX浓度下很明显。添加抗CD 28抗体使细胞对DEX基本不敏感，表明CD 28途径对DEX敏感的转录因子AP-1的依赖性较低。然而，通过CD 2/CD 28触发的T细胞活化的替代途径在研究幼稚细胞时对DEX高度敏感;在记忆细胞的情况下，需要至少10倍高的DEX浓度才能达到相当的抑制作用。DEX对通过旁路途径刺激的初始CD 4（+）T细胞的强烈抑制作用可通过佛波醇肉豆蔻酸酯激活蛋白激酶C（PKC）而完全消除。我们的数据表明，至少有两种不同的机制有助于DEX抗性，即CD 28触发和PKC激活，这可能在记忆细胞中更有效地发生，使它们对DEX不太敏感。
Human CD45RA(+) ('naive') and CD45RO(+) ('memory') CD4(+) T cells were compared with respect to their sensitivity to dexamethasone (DEX). In three different activation pathways, i.e. (i) immobilized anti-CDS, (ii) immobilized anti-CD3 plus soluble anti-CD28 and (iii) soluble anti-CDS plus soluble anti-CD28 naive CD4(+) T cells appeared more sensitive to DEX than memory CD4(+) T cells. In the anti-CD3 system this difference in sensitivity was apparent at a suboptimal DEX concentration. Addition of anti-CD28 rendered the cells largely insensitive to DEX, indicating that the CD28 pathway is less dependent of the DEX-sensitive transcription factor AP-1. However, the alternative pathway of T cell activation through CD2/CD28 triggering was highly sensitive to DEX when naive cells were studied; in the case of memory cells, at least a 10-fold higher DEX concentration was needed to achieve a comparable inhibition. The strong inhibitory effect of DEX on naive CD4(+) T cells stimulated via the alternative pathway was completely abrogated by activation of protein kinase C (PKC) with phorbol myristate acetate. Our data suggest that at least two different mechanisms contribute to DEX resistance, i.e. CD28 triggering and PKC activation, which may occur more effectively in memory cells making them less sensitive to DEX.