INTERLEUKIN-4 AND HUMAN-IMMUNODEFICIENCY-VIRUS STIMULATE LFA-1-ICAM-MEDIATED AGGREGATION OF MONOCYTES AND SUBSEQUENT GIANT-CELL FORMATION

The effects of recombinant interleukin 4 (IL-4) on cell cluster and mu ltinucleated giant cell (MGC) formation from human immunodeficiency vi rus (HIV)-infected and uninfected monocytes were examined. Human blood monocytes were isolated by centrifugal elutriation and monoclonal ant ibody-complement-dependent lysis of residual T cells, and infected wit h low passage HIV strains. Monocytes were exposed to recombinant IL-4 (1 to 20 ng/ml), continuously after inoculation with HIV. Monocyte exp ression of ICAM-1 but not LFA-1 was significantly enhanced by IL-4 alt hough substrate adherence was a more potent stimulus. Monocyte cluster and MGC formation was quantified after fixation and staining with Gie msa. Clusters of HIV-infected and uninfected monocytes were consistent ly and significantly increased at 4 to 7 days after IL-4 stimulation. The combination of HIV and IL-4 was more stimulatory than either treat ment alone. In two out of five uninfected and three out of seven HIV-i nfected monocyte cultures, MGC formation was also markedly increased a t 10 to 14 days after stimulation. Incubation with anti-LFA-1 (anti-CD 11a, anti-CD18) and anti-ICAM-1 (anti-CD54) monoclonal antibodies redu ced IL-4-stimulated aggregation in HIV-infected and uninfected monocyt es and subsequently reduced MGC formation. Anti-ICAM-1 was not as effe ctive as anti-CD11a or anti-CD18 in inhibiting aggregation of HIV-infe cted monocytes and in these cultures anti-ICAM-2 was also inhibitory. Extracellular HIV antigen concentrations were not consistently reduced by anti-CD11a or anti-ICAM-1. Hence IL-4 markedly enhanced monocyte a ggregation in both HIV-infected and uninfected monocytes, probably thr ough enhanced LFA-1-ICAM-1 interactions in all cultures and LFA-1-ICAM -2 interactions in infected monocytes, leading subsequently to MGC for mation in some cultures.