Researchers discover way to dramatically boost the output of immune system cells from the thymus

Sep 26 2005

Mayo Clinic researchers have discovered a way to dramatically boost the output of immune system cells from the thymus, which may lead to improved cancer vaccines, as well as to ways to otherwise strengthen immune responses.

The Mayo report appears in the current online edition of the journal AIDS. Mayo Clinic scientists studied the immune system responses in blood samples from health care workers accidentally exposed to HIV, who then received a commonly used anti-AIDS treatment known as antiretroviral therapy (ART). None of the workers developed HIV infections.

In these non-HIV-infected test subjects, the scientists discovered that ART dramatically increases (up to a factor of 1,000) the production of cells from which the immune system makes disease-attacking T cells. Importantly, the increase in T cells also occurred in older people who generally produce few new T cells. Further experiments were performed in mice to see if the ART treatment caused the immune system to erroneously attack the host instead of disease agents. It did not.

The findings are significant because they suggest new ways to use an existing and approved drug regimen of ART to stimulate the thymus to produce more T cells -- without provoking an "autoimmune" reaction in which the body attacks itself. T cells are major disease fighters of the immune system that are depleted in diseases such as AIDS and cancers, as well as in bone marrow transplant recipients. ART is a combination treatment of antiretroviral drugs and drugs that prevent cell death.

"One of the potential uses we envision is to use the ART treatment as a way to use tumor components to immunize cancer patients against their own cancer cells," explains Mayo Clinic immunologist David McKean, Ph.D. "The current problem with this treatment strategy is that the tumor gives off a variety of soluble products which we don't fully understand, but which we know wreck havoc on the immune system by suppressing its various components. If we can use the ART drugs to increase the number of newly produced T cells in cancer patients first, we can potentially improve the likelihood of getting a cancer vaccine to work."

The findings may also benefit the aging population.

"The ability of ART to boost T cell numbers may allow patients who normally don't respond to vaccines – such as those with chronic disease, or the elderly – to mount an effective immune response if they receive the vaccination in combination with ART," says co-author and Mayo Clinic immunologist Andrew Badley, M.D.

With age the thymus (located in the upper chest) diminishes and produces fewer T cells. This leaves the elderly more vulnerable to disease and less able to make effective use of vaccines. However, researchers say if the aging immune system was primed by the ART regimen prior to receiving vaccines, a stronger immune response might be provoked. That way people might be better protected, and public health officials could use their supplies of vaccine more effectively.

In the seven participants treated with ART, five showed a dramatic increase in a specific kind of cell known as "naive T cells". This is important because naive T cells are used by the body to destroy tumor cells or cells that have been infected by viruses to which the individual has not been previously exposed. Says Dr. McKean, "A person in their 60s doesn't produce many new T cells. Yet in order to effectively respond to a pathogen you haven't seen before, you really need those new T cells produced by the thymus. So that's why as people get older they become more susceptible to particular viruses."