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 EC 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 EC-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 EC 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 EC use LFA-3 to increase early CD40L protein expression on newly activated CD4+ T cells by stabilizing CD40L mRNA.
Murakami
K
K
Molecular Cardiobiology Program, Boyer Center for Molecular Medicine, Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06510, USA.
Ma
W
W
Fuleihan
R
R
Pober
J S
JS
D000276:Adjuvants, Immunologic / Q000502:physiology; D000328:Adult; D018801:CD2 Antigens / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand; D018968:CD58 Antigens / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D014471:Umbilical Veins
D000276:Adjuvants, Immunologic; D018801:CD2 Antigens; D019013:CD40 Antigens; D018968:CD58 Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D023201:CD40 Ligand