Deficient antibody-dependent cellular cytotoxicity against human immunodeficiency virus (HIV)-expressing target cells in perinatal HIV infection

Peripheral blood mouonuclear cells (PBMC) of human immunodeficiency virus ( HIV)-infected children, age-matched HIV-seronegative controls, and HIV-infe cted asymptomatic and symptomatic adults were compared for their ability to mediate antibody-dependent cellular cytotoxicity (ADCC) and natural killer (NK) cell-mediated cytotoxicity against target cells expressing HIV or her pes simplex virus (HSV) antigens, Target cells consisted of CD4 lymphocytes purified from PBMC of HIV-seronegative adults and incubated with the IIIB strain of HIV, HUT78 cells chronically infected with IIIB, and HSV-infected human fibroblasts. PBMC of asymptomatic HIV-infected adults were generally able to lyse CD4 cells expressing HIV antigens. Direct correlation was fou nd between the magnitude of lysis and absolute CD4 cell counts in these ind ividuals. In contrast to these results, PBMC from HIV-infected children wer e generally unable to lyse IIIB-expressing CD4 cells, regardless of the chi ldren's clinical status, age, or absolute CD4 cell counts. Cells from HIV-s eronegative adults and children did not directly lyse these target cells ei ther but, in contrast to cells of HIV-seropositive children, were able to m ediate cell lysis when serum from an HIV-seropositive adult was added. Howe ver, effector cells from these HIV-infected children were able to mediate b oth ADCC against HSV-infected fibroblasts and NK cell-mediated cytotoxicity against DID-infected HUT78 cells. Reduced ability of PBMC from vertically HIV-infected children to mediate ADCC against HIV antigen expressing CD4 ce lls may contribute to rapid progression to AIDS.