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

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 b oth IL-2 and CD40L compared with PHA alone at 6 h, EC are unable to increas e the rate of transcription of CD40L compared with PHA alone as measured wi th 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 ex pression, whereas mAb to ICAM-1 or pretreatment with ICAM-1 antisense oligo nucleotide 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 combina tion with mAb to ICAM-2, does not. We conclude that FC use LFA-3 to increas e early CD40L protein expression on newly activated CD4(+) T cells by stabi lizing CD40L mRNA.