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Interleukin (IL)-2 production after stimulation with human immunodeficiency virus type 1 (HIV-1) envelope (Env) peptides, tetanus toxoid, and phytohemagglutinin was measured in peripheral blood mononuclear cells (PBMC) from 25 HIV-1-infected children with mild and 24 with severe clinical disease and from 15 uninfected children. Env-specific IL-2 production was detected in PBMC of 26.5% of HIV-1-infected children but in none of the uninfected. The absence of Env-specific responses at enrollment among infected children was associated with a 6-fold increased risk of mortality within a year, adjusting for clinical severity (P=.04). Among those with severe clinical disease, Env-stimulated IL-2 reactivity in PBMC was negatively correlated with HIV-1 RNA copy numbers in plasma at enrollment and was positively correlated with CD4 T cell percentages 1 year later. HIV-specific cellular immune responses may play a role in containing progression of HIV-1 infection in children, despite early deficits in cell-mediated immunity.

The expression of the leukocyte adhesion molecule L-selectin (CD62L) on polymorphonuclear neutrophils (PMN) and circulating levels of the soluble form of the receptor (sCD62L) were determined for a group of HIV-1-infected children, categorized as having mild or severe disease, and a group of uninfected control children. The fluorescence intensity of CD62L on PMN was significantly reduced in the HIV-1-infected children with mild disease compared to the uninfected controls. The proportion of lymphocytes expressing CD62L, as well as their corresponding fluorescence intensities, was significantly reduced in both the mild and the severe disease groups compared to the uninfected children, while peripheral levels of sCD62L were significantly elevated in the HIV-1-infected children with mild and severe disease compared to the controls. Altered cell migration resulting from reduced expression of CD62L may be an important contributor to the increased susceptibility to secondary microbial infections seen in HIV-1-infected children.

The polymorphonuclear neutrophils (PMNs) of patients infected with human immunodeficiency virus type 1 (HIV-1) show impaired microbicidal responses. The present study assessed the functional integrity of PMN degranulation responses and the expression of specific receptors that mediate these responses in a group of children vertically infected with HIV-1. PMN degranulation in response to interleukin-8 (IL-8) and complement 5a (C5a) was measured in a group of HIV-1-infected children with mild and severe clinical disease and in an uninfected control group. In addition, the expression of CXCR1, CXCR2, and CD88 on whole-blood PMNs was quantified by flow cytometry. Although CXCR1 expression was found to be largely unaltered in the HIV-1-infected children relative to that in the control children, the intensity of CXCR2 expression was significantly reduced in those with severe disease. Furthermore, there was a significant reduction in the percentage of cells expressing CD88 and in the intensity of CD88 fluorescence in the HIV-1-infected children compared to that in control children, with CD88 fluorescence intensity more significantly reduced in the presence of severe disease. PMNs from a large proportion of the HIV-1-infected children either showed reciprocal degranulation responses or were unresponsive to IL-8 and C5a, whereas the PMNs from the uninfected children showed positive responses. Inefficient agonist-induced degranulation may contribute to the increased susceptibility of HIV-1-infected children to secondary microbial infections. Furthermore, reduced expression of CXCR2 and CD88 may be suggestive of defects in other functions of PMNs from HIV-1-infected children.