rrizzo@bbncca.ARPA (Ron Rizzo) (07/16/85)
[ From the Boston Globe, 7/11 or 12/85. Reprinted without permission.] Study: AIDS Robs Cells Of "Recognition" Ability by Richard Saltus =============================================== [Following close on the heels of another major discovery* :] The first step in the destruction of the immune system by the AIDS virus is a preemptive attack on the ability of key immune cells to recognize foreign organisms, a study shows. The virus acts with such precision that the immune system is utterly unable to mount a response, even though the capacity to counterattack still exists, government researchers said. Thereafter, normal immune competence collapses and the victim is left prey to a wide range of infections and tumors that cause the syndrome's high mortality. The report in today's New England Journal of Medicine adds to the growing evidence on how the AIDS virus - known as HTLV-III or LAV [or ARV] - destroys the very defenses designed to disable it. The virus' name, Human T-Lymphotropic Virus, signifies that it attacks T cells, the white blood cells that orchestrate the complex response of the immune system. The T cells recruit other cells into the fight, cause the release of certain antiinfection substances and stimulate B cells to produce antibodies. AIDS victims have a drastically reduced force of "helper" T cells, called T4, compared to the number of "suppressor" or T8 cells. What has not been clear is whether the low number of T4 cells or some inherent defect in the T4 cells is responsible for the progressive failure of the immune system. Resistance Tested Researchers at the National Institute of Allergy and Infectious Diseases studied blood from 12 AIDS patients, challenging the immune cells with substances that should cause the T4 cells to proliferate rapidly. In this test the T4 cells were not required to recognize a foreign substance. The cells responded normally, showing that they retained the capacity to mount resistance to infection. Then the scientists mixed the blood with a foreign antigen, a protein of the sort that the immune system would encounter should the body be infected by an invading organism. This time there was no response. To the researchers this suggested that the T4 cells, which are equipped to distinguish what is foreign from what is "self," had lost that ability. Dr. H. Clifford Lane, who directed the research, said that the infecting AIDS virus has been shown to attach itself to the T4 receptor, a molecule on the surface of the T4 cell. In effect, the virus blinds the cell to foreign antigens. Lane said it was impossible to be certain whether the virus uniformly knocks out the surface molecule on otherwise intact T4 cells, or perhaps kills off a subpopulation of T4 cells that has the recognition site. In any case, "It's a very smart virus that came up with that way of attacking the immune system," sad Lane. He noted that these events occur early in the disease, leading to a cascade of later abnormalities as the immune system is devastated. No New Therapies Implied Lane, in a telephone interview, said that the discovery does not yet suggest any new therapies for the syndrome, but that it "gives us a better appreciation of how the AIDS virus is attacking and destroying the immune system." In an accompanying editorial, two Harvard scientists said that increasing knowledge about the affinity of HTLV-III/LAV for the T4 cells is helping to explain many of the puzzling aspects of the lethal syndrome - and is raising some concerns. For one thing, said Drs. Richard S. Kalish and Stuart F. Schlossman, when T4 cells multiply to fend off some other infection, they probably become more vulnerable targets to infection by the AIDS virus. This may explain, they said, why exposure to the AIDS virus is less likely to produce the syndrome in the absence of another infection, as in people receiving tainted transfusions and health workers exposed to HTLV-III. However, the Harvard researchers also raised the possibility that, in certain cases, the virus can infect not only T cells but also B cells. "Such virally infected cells may function as a reservoir of virus, potentially thwarting attempts at reconstitution of the immune system," they wrote. While there is still no effective treatment for AIDS, Schlossman said in an interview, "We've learned a great deal about the disease, and the future is not so bleak as one might think." ***************************************************** * In late June the discovery of a gene on HTLV-III which regulates the rate of growth of the virus was announced. HTLV-III displays explosive growth at a rate up to 1,000 times as great as, eg, HTLV-I which is known to cause various cancers. Manipulation of this gene suggests not only possibilities for eventual vaccine production but even for the treatment of people already infected with the virus. So, folks, it probably pays to keep up your general health, to avoid other infections so as to deny the AIDS virus possible footholds in your bodies. Regards, Ron Rizzo