Apoptosis of bystander uninfected CD4+ T lymphocytes by neighboring HIV-infected cells is observed in cell culture and in lymphoid tissue of HIV-infected individuals. This study addresses whether antigen-presenting cells such as human macrophages mediate apoptosis of CD4+ T cells from HIV-infected individuals. Uninfected human macrophages, and to a larger degree, HIV-infected macrophages mediate apoptosis of T cells from HIV-infected, but not from uninfected control individuals. This macrophage-dependent killing targets CD4+, but not CD8+ T lymphocytes from HIV-infected individuals, and direct contact between macrophages and lymphocytes is required. Additional analyses indicated that the apoptosis-inducing ligands, FasL and tumor necrosis factor (TNF), mediate this macrophage-induced apoptosis of CD4+ T cells. These results support a role for macrophage-associated FasL and TNF in the selective depletion of CD4+ T cells in HIV-infected individuals.

Antibodies of the IgM class and IgG2 and IgA2 subclasses are prominent in responses to pneumococcal polysaccharides (PPS) but may be decreased in human immunodeficiency virus (HIV)-infected patients, among whom invasive pneumococcal disease is common. After immunization of HIV-infected and -seronegative subjects with pneumococcal vaccine, the number of PPS-specific antibody-secreting cells (ASC) producing IgM was significantly lower among HIV-infected subjects, whereas PPS-specific IgG and IgA ASC were more comparable. The subclass distribution of PPS-specific IgG2-producing (approximately 80%) and IgA2-producing (approximately 50%) ASC and antibodies in serum were similar. However, before immunization, the proportions of PPS-specific IgG2 for both serotypes 8 and 14 in baseline sera from HIV-infected patients were significantly decreased compared with controls. Thus, the response to PPS among HIV-infected patients may be characterized by lower levels of specific IgG2 before immunization and prominent defects in IgM responses soon after stimulation.

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