HIV infection spreads through the closest of human interactions and now, new research shows that the virus can also take advantage of intimate contacts between cells of the immune system to aid infection of its principal target, the CD4+ T cell.
Dendritic cells (DCs) are the main antigen-presenting cells (APCs) that are involved in the initiation of an immune response. They internalize antigens, which are processed and presented to T cells together with co-stimulatory signals that are essential for T-cell activation. But it seems that HIV has taken advantage of this essential immune interaction: DCs can bind and internalize HIV virions through C-type lectin receptors but, instead of becoming infected, the DCs assist in the infection of T cells. To find out exactly how this happens, David McDonald and co-workers pulsed myeloid-derived DCs with HIV-1, then observed their interactions with T-cell targets using time-lapse fluorescent imaging.
Before T-cell contact, the virus was distributed evenly on or inside the DC but, within minutes, most of it had concentrated in the T-cell–DC contact zone. Internalized HIV was also transported to this site. This redistribution is reminiscent of the formation of structured synapses at the contact region between T cells and APCs. T-cell–DC synapses are a special case, in that they can form in the absence of specific antigen — a process that does not lead to activation but might help T cells to 'sniff out' rare antigen-presenting DCs.
Immunostaining of conjugates between CD4+ T cells and HIV-pulsed DCs showed that CD4 and the adhesion molecule LFA1 (leukocyte function-associated antigen 1) — which are both involved in the antigen-independent synapse — as well as the HIV co-receptors CCR5 (CC-chemokine receptor 5) and CXCR4 (CXC-chemokine receptor 4), were often concentrated at the cell–cell junction. In several of these conjugates, HIV was detected inside the T cell, indicating that infection had occurred across the synapse. This process was even more efficient when the DCs were matured with lipopolysaccharide.
Together, these observations support the idea that HIV has subverted the antigen-independent synapse for its own ends, which takes our appreciation of immune exploitation by HIV to a new level.
ORIGINAL RESEARCH PAPER
McDonald, D. et al. Recruitment of HIV and its receptors to dendritic cell–T-cell junctions. Science 1 May 2003 (DOI: 10.1126/science.1084238)