Early interactions between lung dendritic cells (LDCs) and Mycobacterium tuberculosis, the etiological agent of tuberculosis, are thought to be critical for mounting a protective anti-mycobacterial immune response and for determining the outcome of infection. However, these interactions are poorly understood, at least at the molecular level. Here we show that M. tuberculosis enters human monocyte-derived DCs after binding to the recently identified lectin DC-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN). By contrast, complement receptor (CR)3 and mannose receptor (MR), which are the main M. tuberculosis receptors on macrophages (Mφs), appeared to play a minor role, if any, in mycobacterial binding to DCs. The mycobacteria-specific lipoglycan lipoarabinomannan (LAM) was identified as a key ligand of DC-SIGN. Freshly isolated human LDCs were found to express DC-SIGN, and M. tuberculosis–derived material was detected in CD14−HLA-DR+DC-SIGN+ cells in lymph nodes (LNs) from patients with tuberculosis. Thus, as for human immunodeficiency virus (HIV), which is captured by the same receptor, DC-SIGN–mediated entry of M. tuberculosis in DCs in vivo is likely to influence bacterial persistence and host immunity.

Lymphadenopathy associated virus ( LAV ) has been isolated from patients with the acquired immunodeficiency syndrome (AIDS) or lymphadenopathy syndrome. Since the immune deficiency in AIDS seems to be primarily related to the defect of the helper-inducer T lymphocyte subset, the possibility that LAV is selectively tropic for this subset was investigated. Fractionation of T lymphocytes was achieved by cellular affinity chromatography with monoclonal antibodies. In a hemophilic patient who was a healthy carrier of LAV , reverse transcriptase activity and virus particles detected by electron microscopy were found only in cultures of helper-inducer lymphocytes. When infected with LAV in vitro, lymphocyte subsets from normal individuals yielded similar results. Virus production was associated with impaired proliferation, modulation of T3-T4 cell markers, and the appearance of cytopathic effects. The results provide evidence for the involvement of LAV in AIDS.

Since either macrophages (Mphi) or dendritic cells (DC) differentiate from monocytes (MO) depending on culture conditions, we investigated the relationship of the DC and Mphi differentiation pathways. Culturing MO-enriched blood mononuclear cells with Mphi colony-stimulating factor (M-CSF) or with granulocyte/Mphi (GM)-CSF induced Mphi with a different morphology and CD14/CD1a expression. In contrast, in cultures with GM-CSF and interleukin (IL)-4, cells rapidly became nonadherent and acquired DC morphology, ultrastructure, CD1a expression, and most DC markers; they lost membrane CD14 and CD64 and capacity of phagocytosis, displayed less CD68 than Mphi, but retained nonspecific esterase activity. These DC directly developed from MO without proliferation inasmuch as only day 0 FACS-sorted MO, but not small CD14- cells, differentiated into DC when cultured with GM-CSF and IL-4, or to Mphi with M-CSF While overall cell numbers declined, DC numbers plateaued from culture day 2 onwards, indicating that most had differentiasted by then. This differentiation was radioresistant and occurred without [3H]thymidine incorporation. Commitment to differentiate into DC with GM-CSF and IL-4 was irreversible by day 2, since discontinuing IL-4 at this point did not revert cells to Mphi. Alternatively, cells rapidly converted to DC when IL-4 was added from day 2 to cultures initiated with GM-CSF only. If cultures were initiated with M-CSF and switched to GM-CSF and IL-4 after 2 or 5 days, about half of the cells still converted to DC. Thus, the capacity of MO and even of Mphi to differentiate into DC was conserved for at least this period. The increased capacity to stimulate the mixed leukocyte reaction correlated with the relative number of CD1a+ cells at any time and under each condition tested, a confirmation that these cells functionally qualify as DC. Thus, MO and even Mphi can be directed to differentiate into DC depending on the cytokine microenvironment.