Human endothelial cells augment early CD40 ligand expression in activated CD4+ T cells through LFA-3-mediated stabilization of mRNA

被引:0
|
作者
Murakami, K
Ma, WL
Fuleihan, R
Pober, JS
机构
[1] Yale Univ, Sch Med, Boyer Ctr Mol Med, Mol Cardiobiol Program, New Haven, CT 06536 USA
[2] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06536 USA
来源
JOURNAL OF IMMUNOLOGY | 1999年 / 163卷 / 05期
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暂无
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Human endothelial cells (EC) augment CD40 ligand (CD40L) expression on PHA-activated CD4(+) T cells at early times (e.g., 4-6 h), Fixed EC, devoid of mRNA, are comparable to living EC in their capacity to augment early CD40L expression on CD4(+) T cells. Fixed FC increase T cell mRNA expression of both IL-2 and CD40L compared with PHA alone at 6 h, EC are unable to increase the rate of transcription of CD40L compared with PHA alone as measured with a promoter-reporter gene, although they do increase transcription of an IL-2 promoter-reporter gene. Fixed EC prolong the half-life of CD40L mRNA >2-fold. Inclusion of anti-human LFA-3 (CD58) mAb or pretreatment of EC with an LFA-3 antisense oligonucleotide blocks FC-induced increases in CD40L expression, whereas mAb to ICAM-1 or pretreatment with ICAM-1 antisense oligonucleotide does not. Moreover, mAb to LFA-3 reverses the capacity of FC to prolong the half-life of CD40L mRNA, whereas mAb to ICAM-1, even in combination with mAb to ICAM-2, does not. We conclude that FC use LFA-3 to increase early CD40L protein expression on newly activated CD4(+) T cells by stabilizing CD40L mRNA.
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页码:2667 / 2673
页数:7
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