IN VITRO HIV INFECTION OF DENDRITIC CELL PRECURSORS Effect on Dendritic Cell Differentiation and Function

Cells from the dendritic lineage presumably play an important role in the pathogenesis of human immunodeficiency virus (HIV) infectionu . Langerhans cells (lC), are probably among the first targets for HIV in genital mucosae3.4. later, in T-cell dependent areas of lymphoid organs, dendritic cells (DC) may also be involved in both virus transmission to CD4+ T cells and the generation of an effective anti-HlV immune response2. There is now agreement that mature DC/lC can take up the virus, reverse transcribe its RNA, cluster to and form syncytia with CD4+ T cells, but the real degree of their permissivity to HIV still remains debatedl.5,6. A precise knowledge of the relationships of cells of the DC lineage with H1V is important for understanding AIDS pathogenesis as well as for delineating possible new immunotherapy strategies. Studying their interactions with HIV in different models is therefore warranted. DC are are known to be of hematopoietic origin2•71O • They may be generated in vitro from CD34+ hematopoietic progenitor cells by using combinations of granulocyte/macrophage-colony stimulating factor, tumor necrosis factor-a and stem cell factor7'o. Using such an in vitro differentiation system, we recently characterized a population of CD13hiLin. cells that appears after 5 days of culture and comprise precursors of the dendritic lineage (CD la+) but also of macrophages (CD 14+) and of granulocytes (CD 15+)7,H. CD 13hiLin. cells express CD4 and they are therefore potential targets for HTV. We examined here whether DC precursors are susceptible to HIV, and if DC differentiation and/or function are affected by HIV infection Ill.