Originally created 05/11/02

Theory on HIV's targeting of cell type confirmed



Scientists studying the immune cells of people with HIV have confirmed for the first time that the virus singles out for attack the very cells designed to attack it.

Immune system cells called CD4-plus T cells that are programmed to fight the AIDS-causing virus are two to five times more likely to be infected with HIV than similar immune cells dedicated to fighting other pathogens, federal researchers report Thursday in the journal Nature.

"For years we have known that the immune system does not produce a good CD4-plus T cell response against HIV, and we have theorized this might be because HIV preferentially infects HIV-specific CD4-plus cells. This study is the first to show this phenomenon actually happens in the body," said Dr. Richard Koup, an investigator at the National Institute of Allergy and Infectious Diseases and senior author of the study.

The researchers isolated three subgroups of the immune cells, also called "helper" T-cells, from 12 individuals who were HIV-positive. The groups included HIV-fighting cells, cells dedicated to fighting cytomegaloviruses (herpes-type viruses) and a "mixed" group.

In each patient, HIV infected a much greater percentage of the HIV-specific cells than the other two groups.

"This finding not only helps us better understand how the virus causes disease, it should also aid in developing effective HIV vaccines," said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.

The study found that HIV infects both immature and mature immune system helpers, Koup said.

Four patients who were using an on-again, off-again treatment regimen with antiretroviral drugs were carefully screened to see what happened to their mature helper cells.

When the drugs were stopped, the HIV-specific immune cells rushed in to try and fight the virus, but wound up being infected with HIV at a significantly higher rate than were other types of helper cells.

"So HIV continuously and preferentially infects mature, HIV-specific helper T cells as they try to fight off the virus," said Koup. "In one patient, over half of all his infected CD4-plus T cells were HIV-specific."

Dr. Daniel Douek, the study's lead author, said the findings should cause doctors to consider more carefully the timing and duration of "drug holidays" for HIV patients.

"Although short courses of structured intermittent therapy do not result in increased levels of HIV, longer regimens may result in long-term damage of the immune system's ability to fight off HIV," Douek said.

Douek said the study also suggests that any HIV vaccine must induce response not just from helper T cells, but also from other types of immune system cells that are less susceptible to HIV.

On the Net:

http://www.nature.com

www.niaid.nih.gov