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HIV also kills developing white blood cells.

It's bad enough that the AIDS virus attacks mature white blood cells, rendering them useless for the body's defenses. But now two research teams have discovered that HIV also destroys young immune-system cells before they have a chance to develop. Their reports in the June 24 NATURE- support the notion that HIV does its dirtiest work in lymphoid tissues (SN: 3/27/93, p. 196).

White blood cells called T cells mature and proliferate in the thymus, a small organ that sorts through these cells, destroying those that might attack the body's own tissues. To study whether HIV can infiltrate this T-cell nursery, the two groups implanted human fetal liver and thymus tissue into mice that lack the ability to mount any sort of immune response. In these SCID-hu mice, so called because of their severe combined immunodeficiency defect and their human tissue, the liver makes precursor cells that move to the thymus and develop much as they do in a person.

At the University of California, Los Angeles, School of Medicine, Grace M. Aldrovandl and her colleagues treated a dozen SCID-hu mice with either no virus, inactivated virus, HIV from children with AIDS, or HIV cultured in the laboratory, Seventeen days later, they analyzed the T cells in each thymus implant by staining and sorting through these cells.

In mice that got no active virus, 80 percent of the stained T cells showed both CD4 and CD8 receptors - indicating immature cells -while most of the rest of the cells took up only the CD4 stain. Mice with HIV from children had lost most of the doubly stained cells as well as most of the CD4 cells, the typical HIV targets, the UCLA group reports.

Next, the UCLA researchers injected a much lower dose of different viral strains into additional mice. The T cells disappeared more slowly, and it seems the immature cells were destroyed first, followed by CD4 cells, says Jerome A. Zack, who heads the UCLA group.

Analyses of viral genetic material in these different cell types revealed that the immature cells tended to harbor five to 10 times as much virus per cell as other cells, says Zack. Immature cells divide rapidly, thus providing a way for the virus to replicate rapidly, he adds.

Also, an infected thymus looks different from an uninfected organ, which contains clearly defined rim and core regions. Because so many cells had died in the infected tissue, the researchers had trouble distinguishing the two regions under a microscope, they note.

At SyStemix, Inc., in Palo Alto, Calif., Mark L. Bonyhadl and colleagues also observed that HIV infection spread through the thymus, wiping out most CD4 and immature cells within five weeks. Electron and light microscopy revealed that many cells seemed to undergo programmed cell death (SN: 11/21/92, p.344). HIV may subvert this normal process in the thymus by triggering destruction in cells that otherwise would have been spared, says immunologist Joseph M. McCune of SyStemix.

Both research teams caution that they do not know how well these results translate to AIDS in humans, but they expect the SCID-hu mouse will prove useful for studying HIV in living organisms and may help scientists understand how HIV harms E. Pennisi the immune system.
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Title Annotation:HIV invades thymus in mice, killing immature T cells
Author:Pennisi, Elizabeth
Publication:Science News
Article Type:Brief Article
Date:Jun 26, 1993
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