Induction of functional CD154 (CD40 ligand) in neonatal T cells by cAMP-elevating agents

A deficiency of neonatal T lymphocytes to express CD154 antigen in response to ionomycin and phorbol 12-myrsistate 13-acetate (PMA) stimulation or aft er CD3 cross-linking has been described. In the present report we describe that CD45RA(+) newborn cells are able to synthesize and express CD154 at si milar or even higher levels than adult cells in response to ionomycin and c AMP-elevating agents which trigger the protein kinase A (PKA) -mediated met abolic pathway. Peak CD154 protein concentrations in newborn cells were fou nd between 4 and 8 hr after stimulation with ionomycin and dibutyryl cAMP. These agents, however, did not induce expression of the early activation an tigen CD69. Surface levels of CD154 did not correlate with specific mRNA co ncentration, indicating that dibutyryl cAMP up-regulates CD154 by acting at a posttranscriptional stage. The CD154 antigen induced by PKA activation o f newborn cells was functional, since upon binding to CD40 on B lymphocytes in the presence of interleukin-4 (IL-4), it promoted immunoglobulin heavy- class switching to IgE. We also found a different pattern of cytokine produ ction between neonatal and adult CD4(+) T cells. In response to ionomycin a nd dibutyryl cAMP, cord blood cells were more prone than adult lymphocytes to secrete the T helper type 2-derived immunosuppressive cytokines IL-4 and IL-10. Taking into account that the fetomaternal environment is rich in cA MP-elevating agents, the reduced risk of graft versus host disease associat ed with cord blood trasplantation, as compared with the risk with adult bon e marrow cell transplants, may be due to the bias of neonatal cells to diff erentiate towards the T helper type 2 functional cell subset.