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HIV attack destroys immune innocence.

In a world where it is best to "know thine enemy," naivete should be a fatal flaw. But cells of the immune system need a certain innocence in order to fight new invaders. After the battle, they carry a "memory" of their bacterial or viral foe and remain alert for its next attack.

While HIV infection is marked by a general decline in the number of immune cells, new evidence indicates that the virus may scuttle the immune system by destroying naive immune cells that have yet to taste battle. The findings, reported by Stanford University Medical Center researchers in the May Journal of Clinical Investigation, may help doctors track the progression of AIDS but could have ominous implications for therapies.

All immune cells originate in bone marrow. A subset, the T cells, migrates to the thymus and develops into a variety of naive helper (CD4) and killer (CD8) cells -- two kinds of immune cells that work in concert to fight infection. Released from the thymus and exposed to the antigens of invaders, T cells become memory cells and respond only to future attacks by the same invader.

All T cells carry characteristic protein markers on their surfaces. HIV, the AIDS-causing virus, infects them by recognizing the marker for CD4 cells.

Currently, physicians track the progress of HIV infection by measuring the decline of CD4 cells. But some patients with very low CD4 counts remain well, while others with relatively high counts die quickly. Stanford immunologist Mario Roederer says that although CD4 counts may predict a mean time to death, they represent "a very poor marker of the disease for an individual."

The Stanford researchers, led by Leonard A. Herzenberg and Leonore A. Herzenberg, decided to focus only on naive T cells. They marked T cells with fluorescent antibodies specific to three surface protein markers -- either CD4 or CD8, plus two markers specific to naive cells. The combination of markers distinguishes naive helper and killer T cells from their memory counterparts.

The group compared the numbers of naive T cells in 266 HIV- infected adults with the counts for 44 uninfected adults. Fifty percent of the T cells in normal adults were naive, as opposed to only 10 percent in HIV-infected participants. Roederer claims he saw a "pronounced effect" with the first few patients.

The Stanford team found similar numbers of CD8 cells in the two groups. Strikingly, however, less than 15 percent of the CD8 cells in HIV-infected individuals were naive, compared to 50 percent for the control group. The team also reports similar results in children.

Roederer and Leonard Herzenberg speculate that HIV disrupts the balance between naive and memory CD8 cells by infecting them in the thymus before they have fully matured. They suggest that counting naive cells could better predict the course of AIDS for individuals.

However, because the body needs naive cells in order to mount an immune response to new bacterial and viral threats, current therapies designed to stimulate immune responses against HIV could be doomed to failure. "We may have to rethink our approaches to HIV," says Herzenberg.

Though encouraged by the Stanford group's finding, Jonathan M. Kagan of the National Institute of Allergy and Infectious Diseases in Bethesda, Md., warns that they may be "observing the result of an overall activation of the immune system" due to HIV infection rather than destruction of naive T cells.

Herzenberg hopes to continue the work to determine whether decreases in naive T cells correspond closely to disease progression.
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Title Annotation:Hiv virus kills naive helper cells
Author:Seachrist, L.
Publication:Science News
Date:May 6, 1995
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