Abstract 1576 Neonatal Infectious Disease Platform, Monday, 5/3

Introduction: Virally-induced alterations in fetal/newborn immune function may play important roles in mother-to-child transmission of HIV-1. In particular, the chemokine receptors CXCR-4 and CCR-5 have recently been shown to be co-receptors for HIV cell entry, and the costimulatory molecules B7-1 and B7-2 deliver critical second signals in immune activation. The effects of HIV proteins on these critical immunoregulatory cell surface proteins on neonatal immune cells has not been well delineated.

Methods: To investigate the effects of HIV-1 proteins on immunologically important cell-surface proteins, we isolated umbilical cord blood mononuclear cells (CBMC) from 10 healthy term newborns. CBMC were co-cultured with HIV-1 Nef and Tat proteins, and flow cytometric analysis was performed after 48 hours of culture. The surface expression of CD14, CD4, the costimulatory molecules B7-1 and B7-2, and the chemokine receptors CXCR-4 and CCR-5 was measured.

Results: Incubation of CBMC with Nef, but not Tat, resulted in upregulation of CD14 expression on monocytes. B7 isoform expression on monocytes was differentially affected by Nef: B7-1 expression was upregulated and B7-2 expression was downregulated, compared to cells cultured in medium alone, following incubation with Nef. Tat did not alter expression of either B7 isoform. Nef had differential effects on chemokine receptor expression depending on the cell type studied: Nef downregulated both CXCR-4 and CCR-5 expression on monocytes, but upregulated CXCR-4 (but not CCR-5) expression on lymphocytes. Tat had no effect on either chemokine receptor on either cell type. Nef decreased expression of CD4 on cord blood lymphocytes, an effect which has been previously reported in adult lymphocytes. Neither B7 isoform was detectable on lymphocytes, and neither HIV protein altered their expression.

Conclusions: These results suggest that the immunopathogenesis of HIV/AIDS in newborns is mediated in part via alterations in immunoregulatory proteins on lymphocytes and monocytes. Further exploration of these effects, along with comparisons to adult cells, will better define the immune factors which control HIV vertical transmission and HIV/AIDS disease progression in infants and children.