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We have investigated several aspects of nonspecific immunity in Down syndrome (DS), utilizing peripheral polymorphonuclear leukocytes (PMNL), obtained from 12 children aged 8-16, diagnosed as trisomy 21, and their healthy matched controls. We used the under agarose method for chemotaxis assays, and flow cytometry for the determination of phagocytosis of monodispersed fluorescent beads, metabolic burst activity, and neutrophil surface marker expression on these cells. Our results indicate that a chemotactic defect exists in PMNL of DS children. However, no statistically significant differences were found between PMNL from DS children and those from controls in phagocytosis, oxidative burst, and expression of the markers CD11a, CD11b, CD16, and CD 18. Furthermore, no overexpression of CD11a and CD18 was present as a consequence of gene overdosage in PMNL from DS children. On the other hand, 3 different neutrophil subpopulations could be observed according to the CD16 staining pattern in DS children and controls; this might be a consequence of genetic variation or may represent different states of activation of these cells. Other factors such as T-cell involvement, and the role of cytokines, cyclic nucleotides, and zinc serum levels in DS patients should be further investigated in order to define the causes of the immunological derangement present in this condition.

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The phenomenon of apoptosis observed in lymphoid cells from HIV+ subjects is an important factor contributing to their massive depletion. Several studies have identified nitric oxide (NO) as one of the molecules involved in the apoptosis phenomenon observed during HIV infection. It has been shown that HIV-derived gp120 enhances NO synthesis in cultured cells from HIV+ individuals. Therefore, we tested the potential of two nitric oxide synthase (NOS) inhibitors with different mechanisms of action as preventive agents of in vitro apoptosis, in peripheral blood mononuclear cells (PBMC) from HIV+ subjects. PBMC isolated from these patients always showed higher apoptosis levels than normal subjects, a fact that correlated with overproduction of NO and with reduction of mitochondrial transmembrane potential in these cells. We identified the CD8+ T lymphocyte sub-population as the major apoptosis target in PBMC cultures. Treatment with NO inhibitors N(G)-monomethyl-L-arginine (L-NMMA) and dexamethasone (DEX) inhibited spontaneous and mitogen-induced apoptosis, while reducing mitochondrial alterations in PBMC from both normal (30%) and HIV+ (70%) subjects. The development of apoptosis in target cells correlated with their mitochondrial transmembrane potential impairment and with increased expression of Fas (CD95) molecules. These results offer additional alternatives for the manipulation of cellular depletion in HIV disease.