PROGRESSIVE IMPAIRMENT OF MONOCYTIC FUNCTION IN HIV-1-INFECTED HUMAN MACROPHAGE HYBRIDOMAS

Using human macrophage hybridomas infected with HIV-1, we investigated monocyte function over a 5-week period after HIV-1 infection. Two clo nes, 63 and 30, were infected with HIV-1IIIB. Infection was documented by RT activity (15 x 10(6) cpm/ml), intracytoplasmic staining with an anti-p24 antibody, in situ hybridization with an HIV-1-specific ribop robe, and electron microscopy showing intracytoplasmic virus. Two week s after infection, clones 63 and 30 lost expression of all class II an tigens (DR, 81.7 vs. 0%; DQ, 15.6 vs. 0%; and DP, 76.9 vs. 0%) while r etaining expression of class I (87.4 vs. 84.1%), LFA-1 (82.4 vs. 83.1% ), and LFA-3 (79.1 vs. 74.7%) antigens when compared to uninfected cel ls. When tested for functional integrity, infected but not uninfected clone 63 cells failed to stimulate a tetanus-specific MHC-restricted T cell proliferative response 2 weeks after infection. Cytokine secreti on and antigen processing were also perturbed as production of IL-1 wa s abolished 2 weeks after infection (although IL-6 secretion was augme nted) and infected clone 63 cells failed to process exogenous antigen. Last, the viability of T cells cocultured with infected clone 63 was dramatically decreased 35 days after infection (85 vs. 15%). There was no evidence of transmission of HIV-1 to T cells, suggesting a toxic e ffect of infected clone 63. Taken together, these data suggest that al tered macrophage function in our system occurs at multiple levels, whi ch may account for the early immunological defects described in HIV-1 infection.