Expression and Regulation of B7 Family Molecules on Macrophages (MΦ) in Preterm and Term Neonatal Cord Blood and Peripheral Blood of Adults

Abstract

Background: Macrophage (MΦ) receptors of the B7 family (CD80, CD86) play a crucial role in T cell activation: the lack of costimulation leads to anergy or apoptosis of reactive T cells. MΦ may differentiate into different subsets, the balance of which defines MΦ-dependent T cell reactions. The aim of this study was to examine neonatal and adult T cell response with respect to the costimulatory MΦ-potential in order to identify molecular predictors for the neonatal immune defense. Methods: MΦ from peripheral blood (PBMΦ) or cord blood (CBMΦ) were stimulated with interferon-gamma (IFN-γ), cyclic adenosine monophosphate (cAMP), CD40 ligand (CD40L), of αCD3. Results. As compared to PBMΦ, CBMΦ showed a significantly decreased upregulation of CD80 and/or CD86 after stimulation with IFN-γ, cAMP, CD40L, and αCD3. Accordingly, the proliferative T cell response was impaired in the presence of CBMΦ. The fraction of T cells that underwent cell death was higher, and blast formation was significantly lower than that observed in the presence of PBMΦ. Conclusions: CBMΦ, as compared to PBMΦ, delivered fewer costimulatory but more cytotoxic signals to T cells. These observations suggest that MΦ are one factor explaining the suboptimal immune defense of neonates and their increased susceptibility to infection. Using the costimulatory MΦ-potential as a predictor for immune responses requires a separate reference value system in neonatology. © 2003 Wiley-Liss, Inc.