CD4 EXPRESSION ON DENDRITIC CELLS AND THEIR INFECTION BY HUMAN-IMMUNODEFICIENCY-VIRUS

Infection of dendritic cells (DC) by human immunodeficiency virus (HIV ) has been disputed. Employing a fluorescence-activated cell sorter, D C, identified by the absence of membrane markers for T, B, natural kil ler (NK) and monocytic cells and by high levels of MHC class II DR ant igen, were shown to express low levels of CD4. Immunomagnetic beads we re used to separate blood low density cells, which are enriched for DC , into CD4-positive and -negative populations, Examination of these ce lls by electron microscopy showed an increase in the percentage of cel ls with DC morphology in the CD4-positive fraction and a reduction in the CD4-negative fraction. Electron microscopy of semi-purified DC pre parations infected in vitro for 5 days with HIV-1 revealed morphologic ally distinct veiled DC with mature virions on the cell surface and vi rus budding through the cell membrane. Further evidence for the growth of HIV in DC was provided by experiments in which DC were extensively depleted of contaminating lymphocytes and monocytes prior to infectio n. Estimation of provirus load by a nested PCR indicated that after 5 days an infection level of one provirus copy per five cells could be a chieved. After 7 days the provirus copy number could exceed the cellul ar genome copy number, suggesting that some cells had more than one pr ovirus. Infectious virus could not be demonstrated in these cultures a fter 24 h but was detected after 5 or 7 days. Infection of DC in the p resence of antibodies against CD4 was inhibited and suggests infection occurs via a CD4-dependent pathway. These results confirm that DC are susceptible to HIV infection in vitro. The immunological consequences of DC infection in vivo may be significant in the pathogenesis of AID S.