Researchers from the University of Pittsburgh School of Public Health have found that an inheritable trait, in which dendritic cells of the immune system have low levels of cholesterol, slowed the usually rapid spread of HIV from dendritic cells to T cells. Dendritic cells are one of the first lines of defense of the interior immune system, patrolling the skin and mucus membranes for pathogenic agents. Usually, they are able to engulf the pathogen and transport pieces of it back to the lymph nodes, where the body responds by producing T cells, antibodies, and other immunologic agents to combat the pathogen. In HIV however, the virus hitches a ride on the dendritic cell until they travel to the lymph node, where the HIV transfers itself to the T cell and begins the full viral infection.
The study took data from a 30-year longitudinal analysis of anonymous patient samples and reports from the Pitt Men’s Study, part of the national NIH-funded Multicenter AIDS Cohort Study (MACS). It had been previously noted that certain individuals infected with HIV demonstrate a disease progression that is uncharacteristically slow, even when analysis controlled for age, general health, and other factors. By slowing the rate that HIV jumps from dendritic cells to T cells, these individuals were able to stay off medication for a longer time after initial diagnoses and did not need such high doses for a portion of their treatment regimen.
Eight individuals who showed this delayed onset of AIDS, deemed “nonprogressors”, were studied compared to eight typically progressing individuals infected with HIV. All participants were assessed twice a year for a span of 11 years. The researchers found that dendritic cells (and B cells, which also can transfer HIV to T cells) contained far less cholesterol in nonprogressors than typically progressing individuals, even though the blood from both groups contained similar blood cholesterol levels. This led to an undetectable level of HIV transfer from B or dendritic cells to T cells.
Cholesterol is a component of all cell membranes in the human body. Because HIV attaches to B and dendritic cells membranes, the researchers postulated that the decrease in cholesterol decreased the ability of the HIV to bind to the membranes of these immune cells, preventing transportation to the lymph nodes, and ultimately transfer to T cells. Indeed, when HIV was mixed directly with T cells of the nonprogressors, the cells became infected at the same rate as the typically progressing individuals, showing that the cholesterol effects were occurring at the B and dendritic cell level. Says Charles Rinaldo, Ph.D., chairman of Pitt Public Health’s Department of Infectious Diseases and Microbiology, and professor of pathology, “Understanding how this works could be an important clue in developing new approaches to prevent progression of HIV infection.”