Abstract 64

Background: Costimulatory macrophage-receptors of the B7-family(CD80 and CD86) play a crucial role in the CD28 T cell activation pathway. A second function of MΦ is the destruction of T cells. We previously found that MΦ may differentiate into two functionally and phenotypically distinct populations: A T cell stimulating type (MI), being able to upregulate receptors of the B7-family, and a MΦ with cytotoxic potential(M2), which fails to upregulate costimulatory receptors but instead expresses a high density of the Fc-gamma III-receptors (CD16). Forming cellular conjugates through antibodies or immune complexes, targeted T cells are deleted via apoptosis. Stimulation with IFN-γ favours the first MΦ differentiation pathway, Interleukin-10 (IL-10) favours the latter. The two pathways are mutually exclusive. Aims: Investigation of the costimulatory and cytotoxic potential of neonatal MΦ. Methods: Peripheral blood MΦ (PBM) from healthy adults (n=14) and cord blood MΦ (CBM) from preterm (n=4) and term neonates (n=10) were isolated and phenotyped fluorometrically. In tissue culture cells were stimulated with different concentrations of IFN-γ or IL-10 for up to 48 hours. Results: Compared to PBM, isolated CBM showed an up to 70% decreased receptor-upregulation of CD80 and CD86 after stimulation with IFN-γ. CBM of preterm neonates had phenotypical and functional similarities with the M2-type MΦ, expressing higher levels of CD16 and reacting with a higher sensitivity to IL-10. Coculturing MΦ with adult T-cells in the presence of the T cell mitogen anti-CD3, CBM not only lead to less blast formation, but preferentially deleted targeted T cells after stimulation. Conclusions: Under our experimental conditions, CBM delivered less costimulatory but more cytotoxic signals to T cells. These observations may have relevance concerning the increased susceptibility of severe infection in premature neonates.