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.