New AIDS Data Explains T-Cell Puzzle, Suggests New Treatments, According To University Of California Researchers

February 03, 1998

BERKELEY, Calif. -- Besides preventing HIV from killing T-cells, anti-retroviral treatments may increase the body's ability to generate new cells in some patients, according to recent data from a new diagnostic technique developed by UC Berkeley and UC San Francisco researchers. The technique allows human cells, including T-cells, to be directly traced from the time they are created until they die.

T-cell death versus production is an ongoing debate in the AIDS community. Strategies for preventing or reversing immune deficiency depend on knowing what makes T-cell count fall.

Previously many researchers believed the underlying cause of AIDS, which is immune deficiency, could best be explained by abnormally high rates of cell death that forced the immune system to battle back with high rates of new cell generation. But the availability of the new technique has revealed an important role for the T-cell production systems as well. It found T-cell production rates were higher in patients on potent protease inhibitor treatments.

"Our research shows that T-cell count in AIDS patients on protease inhibitor treatments is closely related to the number of cells their body can produce each day," said Marc Hellerstein, M.D./Ph.D., associate professor of nutritional sciences at UC Berkeley and associate professor of medicine at UC San Francisco. "T-cells do have a shorter life-span in AIDS than in healthy people, but the production of new cells is also an important factor in determining T-cell counts."

Hellerstein will present the data Tuesday, February 3 at 10:45 a.m. Central Standard Time (8:45 a.m. Pacific Standard Time) at the 5th Conference on Retroviruses and Opportunistic Infections in Chicago. A description of the new technique was published in the Jan. 20 issue of the Proceedings of the National Academy of Sciences. Joseph M. McCune, M.D./Ph.D., of the Gladstone Institute of Virology and Immunology at UC San Francisco collaborated in the studies, conducted with AIDS patients at San Francisco General Hospital.

AIDS is caused by the retrovirus HIV. Like many other viruses, HIV enters human cells in order to reproduce, since viruses cannot replicate on their own. It attacks and gains entry to cells that have CD4 receptors on their surface. The most significant of these are helper T lymphocytes, or T-cells, which respond to foreign substances and perform critical functions in warding off infections.

From the time the virus is first detectable, it begins to replicate in T-cells. This replication eventually destroys the cell. However, in early stages of the infection T-cell levels generally remain near normal. This may be because the immune system is still able to churn out new cells to replace those that are destroyed. This period of the disease is the so-called dormant stage since few symptoms are apparent and it can last years.

Eventually, however, T-cells are destroyed more rapidly than the immune system can produce them, causing a drastic reduction in their number. The result is a serious impairment of the immune system and increased susceptibility to opportunistic infections, a hallmark of full-blown AIDS.

The body's T-cell stores in AIDS have been compared to a sink with the drain wide open and the faucet on full force. "The big question has been, is there a reason to turn up the faucet, if the drain is still wide open?" said Hellerstein. "Well, now we have reasons to believe that the faucet is involved, as well."

Hellerstein and McCune came to this conclusion by tagging T-cells using deuterium, or "heavy" hydrogen, to label DNA in T-cells as they are produced. Deuterium is a non-radioactive, and thus safe, hydrogen isotope double the weight of regular hydrogen. It can only be detected in newly generated DNA by mass spectrometry and affords a very reliable count of the number of new cells generated.

In the past, cell generation could not be directly measured because techniques involved radioactive or toxic chemicals unsuitable for human consumption. The availability of a safe, reliable method for measuring the rate of cell generation in humans is expected to be useful in a number of diseases.

Use of this technique in AIDS patients revealed tremendous individual variability, said Hellerstein. Some patients have an impaired T cell regeneration system, while other patients make extremely high numbers of T cells. Also, some patients responded to protease inhibitor therapy with high T-cell production rates and improvement of T-cell counts, he said, while other patients did not get a boost in their T-cell counts, despite suppressing the virus. These latter individuals were unable to increase T-cell production rates. Still other patients developed resistance of the virus to protease inhibitors, but maintained high T-cell counts. They were found to be producing tremendous numbers of T-cells each day. These different response patterns might represent clinically useful sub-groups of patients, says Hellerstein.

"Identification of patients who have good virologic control but cannot generate more T-cells may suggest the need for immunostimulatory therapies in addition to antiviral drugs, for example," he said. Such therapies might include transplanting immune stem cells or thymic tissue, or administering agents such as interleukin-2.

UC Berkeley has applied for a patent on the new technique and SpectruMedix Corporation of State College, Pennsylvania, has acquired rights to the technique. SpectruMedix is a U.S. company producing medical and scientific technologies and associated instrumentation.

The technique is expected to be useful for treatment of a wide variety of diseases, including AIDS, cancer, heart problems and osteoporosis. It allows physicians to safely and rapidly measure the efficacy of particular drug therapies in individual patients and gives physicians the ability to tailor treatment based on individual response to the drug. The test is not yet commercially available to physicians.

University of California - Berkeley

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to