title: CD40 ligand is expressed and functional on activated neonatal T cells.
abstract: Deficient CD40 ligand (CD40L) expression by neonatal T cells has  been proposed to explain the diminished Ig production by newborns. Therefore, we examined the expression and function of CD40L on activated neonatal CD4+ T cells isolated from cord blood. Anti-CD3 activation of neonatal T cells resulted in the expression of CD40L demonstrated with specific mAb or a soluble CD40.G1 construct. The level of expression was comparable to that of adult memory CD4+ T cells. In contrast, PMA and ionomycin induced only minimal CD40L expression by neonatal T cells, whereas adult memory T cells expressed CD40L comparably after stimulation with PMA and ionomycin or anti-CD3. The expression of CD40L was blocked by cyclosporine and prostaglandin E2 (PGE2). IL-2 IL-4 partially reversed the inhibition of CD40L expression by cyclosporine, and IL-2 reversed the inhibition by PGE2. CD40L expressed by neonatal T cells was functionally active, since neonatal T cell-dependent production of IgG4 and IgE was inhibited by a soluble CD40.G1 construct. Moreover, neonatal T cells supported the secretion of significantly more IgG, IgA, and IgE than CD40L-deficient hyper-IgM T cell clones. In addition, neonatal CD4+ T cells induced CD86 B7-2) expression by neonatal B cells that was blocked by anti-CD40L but not by control mAb. The results indicate that neonatal T cells activated through the TCR/CD3 complex express CD40L and use it to promote CD86 expression, Ig secretion and heavy chain isotype switching by neonatal B cells.
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Splawski
authors.forename: J
authors.initials: J
authors.lastname: Nishioka
authors.forename: Y
authors.initials: Y
authors.lastname: Nishioka
authors.forename: P E
authors.initials: PE
authors.lastname: Lipsky
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001483:Base Sequence; D017252:CD3 Complex / Q000276:immunology; D019013:CD40 Antigens / Q000378:metabolism* / Q000502:physiology*; D023201:CD40 Ligand; D016572:Cyclosporine / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D005312:Fetal Blood / Q000276:immunology*; D006801:Humans; D007231:Infant, Newborn; D015759:Ionomycin / Q000494:pharmacology; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology*; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D019013:CD40 Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D015759:Ionomycin; D016572:Cyclosporine; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate