Maintain Your T-Cell Count, and Get More T-Cells
May 1, 2000
AIDS is an illness that may be caused by having too few T-cells able to fight infections. Sixteen years ago, a group of scientists at the National Institutes of Health (NIH) began looking for a way people with HIV could protect the T-cells they still have and get more. They may have succeeded.
A Theory of How HIV Causes AIDS
One way the body protects itself from diseases caused by germs is to kill the cells that are infected by the germs and wipe up the germs that are floating around outside of cells with a kind of sticky sponge called an "antibody." In order to eliminate the cells that are infected, the body produces a particular kind of white blood cell that kills infected cells. This cell, called a cytotoxic lymphocyte (CTL) or CD8+ T-cell acts like a soldier and kills infected cells. However, it does not do its job well without assistance from a T-helper cell. The assistance that T-helper cells give can only happen if the T-helper cells recognize the specific germ in the body.
As your immune system develops from childhood on, you produce billions of T-helper cells, each a little different, like the letters of the alphabet. Each of these sets of T-cells recognizes surface markers on cells, or antigens (the footprints that germs make). When your cells are infected with a germ, the infected cells express these antigens and an army of T-helper cells are mobilized and tells the killer CD8+ cells to attack. At the same time they tell the other cells to make lots of antibodies that are specifically designed to mop up that germ.
HIV attacks these helper cells, and ironically, your body gets rid of these HIV infected T-helper cells. The body makes more new T-helper cells, but for some reason not yet fully understood, its ability to replace these T-helper cells gradually fades, and you eventually start losing "letters" from your T-helper cell alphabet. We could call the range of all the possible "letters" or the range of all the possible kinds of enemies or targets that T-helper cells can recognize, the "T-cell repertoire." By slowly depleting this repertoire HIV ultimately results in the infections of AIDS.
For example, suppose there is a disease called "zebra." Well, when HIV gets rid of your "z" helper cells, the body might still recognize the zebra germ by spelling out "white horse with stripes" but if it loses the "w" and an "s" helper cells then maybe the body will not be able to realize that the zebra germ is attacking you.
When you get diseases that the body should recognize and fight but does not, it may well be because the body has lost the T-helper cells that can recognize that disease, and this would explain why strange diseases (with few "letters" that can describe them) tend to be first on the list of opportunistic infections.
Up until now, the only way we have found that can help stave off AIDS, and death, has been to try to stop the virus from reproducing. We have invented many different drugs, the "nucleoside analogues" the "NNRTI's" the "protease inhibitors," the "fusion" inhibitors, and the "nucleotides" and we are continuing to push the envelope of drug designs at different targets like the long hoped for "integrase" inhibitors. All of these drugs do ONE thing: they stop HIV from reproducing. They stop HIV from making copies of itself inside T-helper cells, which HIV takes over and uses, as factories for new virus particles.
Given this theory of how AIDS works, it makes sense that scientists would try to figure out a way to protect the "T-cell repertoire." In other words, to make sure that the body has an intact alphabet ready to fight any new disease that attacks it. If the scientists can do this, maybe HIV itself would be irrelevant. After all our bodies live with lots of viruses that do not hurt them. HIV exerts its damage mainly by causing the destruction of the T-cell repertoire allowing the development of opportunistic diseases. Some of the first experiments, which focus on protecting the T-cell repertoire, are about to begin.
Over the years, immunologists have slowly come to understand the immune system better. One big discovery is that the cells of the immune system "talk" to each other. Some of this "talk" consists of proteins called "cytokines" which cells excrete. Scientists have discovered many of them. One very important of these "cytokines" is called Interleukin-2 or IL-2 (there are many interleukins) and it does something rather spectacular. If you put it in a tub with a few T-helper cells, it causes them to make many copies of themselves -- in fact BILLIONS of copies of themselves. It appears that T-helper cells give off IL-2 when they recognize an enemy, and that IL-2 may be one of the ways that T-helper cells make enough copies of themselves to orchestrate a war against the germ.
It is natural that scientists would try out using IL-2 as a way to treat people with HIV and to possibly prevent progression to AIDS. Dr. Kendall Smith, who is Chief of Immunology at The New York Presbyterian-Cornell Medical Center, first identified the IL-2 molecule in 1981. Dr. Smith's work showed that IL-2 binds to IL-2 receptors and directly cause the growth and affect in a positive way the functioning of many cells, most importantly in this case, T-helper cells and T-killer cells, the CD8's, and the Natural Killer (NK) cells.
The earliest efforts to use IL-2 in patients suffering from AIDS were described in 1984 by Dr. Cliff Lane at the National Institutes of Health; IL-2 had first been used by Drs. Steven Rosenberg and Michael Lotz at the National Cancer Institute for the treatment of cancer. Progress was slow, and initial results were not very remarkable. By 1994, Dr. Richard Davey and others in Cliff Lane's laboratory had figured out how to use IL-2 successfully to raise the number of T-cells.
At the present time, lower amounts of IL-2 are being used intermittently to achieve pretty spectacular increases in T-cells. One way of using the therapy involves a cycle of five days every eight weeks of IL-2. In many cases, after the T-cell count has risen significantly, the T-cell count can be maintained well into the 'normal' range with therapy as infrequently as once a year. From studies it appears that much of the T-cell repertoire is produced and that the cells produced appear to function normally. The side effects of IL-2, which were quite serious in the early days when people were not clear on how to use IL-2 have become more manageable on the lower dose regimens.
Reasons for Hope
There are suggestions in some of the data from clinical trials so far that:
Figure it Out
There is really only one way to find out if something works. If IL-2 protects people from getting opportunistic infections and protects the T-cell repertoire it may ultimately serve as an alternative to antivirals for some people. We can only find this out by trying it out. For this reason there are several trials going on nationally, two in particular. The "SILCAAT" trial 1-800-CHIRON8 (for people with low T-cells, below 300) and the "ESPRIT" trial 1-800-AIDS NIH (for people with higher levels of T-cells, over 300). Both trials involve thousands of people. In addition, there are trials ongoing in New York City at The New York Presbyterian Cornell Medical Center. If you are interested in trying out IL-2 and getting your T-cells up, and helping us figure out if this method works, then please consider joining a study.
In New York, Silcaat sites include: NYU/Bellevue - 212-263-6565, Beth Israel - 212-420-4519, Liberty Medical - 212-243-1980 and Dr. Gervais Frechette at 212-929-2629.
We ALL need to figure this out not only because it is important to have every kind of therapy that works available to us, but this particular therapy is inexpensive enough that if it works without antivirals, which is one possibility, it would be affordable in poor countries where millions of people have already died from HIV without ANY medicines.
Two uniquely informative and easy to understand educational pieces on immune based therapies and IL-2 will be available in mid-June 2000. Community Prescription Service (CPS), the HIV-positive owned and operated mail-order prescription service is producing the "Immune City" issue of InfoPack (bound by POZ) and a booklet called Immune Restoration in HIV. To obtain free copies, call CPS at (800) 842-0502 or go to their website, www.prescript.com, for download of both.
David Scondras is the founder and chairman of Search For A Cure. Scondras developed the nationally recognized HIV treatment series, Reasons for Hope. All articles in the series are reviewed by expert HIV doctors and scientists and an HIV positive and negative focus group to ensure both accuracy and understandability.
Community reviewers include: Matthew Daloisio, Stuart Pynn, Dede Ketover and Robert Krebs.
The Scientific Review Panel for this article includes: Dr. Alfred DeMaria, Massachusetts Department of Public Health; Dr. Kendall Smith of Cornell University Medical School, Dr. Ronald Mitsuyasu of UCLA, and Dr. Fred Valentine of New York University Center For AIDS Research.
If you have any questions or would like to receive the Reasons For Hope series contact Search For A Cure at 34 Edgerly Road #1, Boston, MA 02115 or call Search For A Cure at 617-536-2474 or fax 617-266-0051, or e-mail at email@example.com. Visit our web site at www.searchforacure.org
Search For A Cure is a not for profit organization providing education, promoting access & advocating the basic human right to safe and effective treatment for all people living with AIDS.
This article was provided by Search for a Cure. It is a part of the publication Reasons for Hope.