ROCHESTER, Minn. -- Mayo Clinic researchers have discovered a way todramatically boost the output of immune system cells from the thymus,which may lead to improved cancer vaccines, as well as to ways tootherwise strengthen immune responses.
The Mayo report appears in the current online edition of the journal AIDS, (http://www.aidsonline.com).Mayo Clinic scientists studied the immune system responses in bloodsamples from health care workers accidentally exposed to HIV, who thenreceived a commonly used anti-AIDS treatment known as antiretroviraltherapy (ART). None of the workers developed HIV infections.
In these non-HIV-infected test subjects, the scientistsdiscovered that ART dramatically increases (up to a factor of 1,000)the production of cells from which the immune system makesdisease-attacking T cells. Importantly, the increase in T cells alsooccurred in older people who generally produce few new T cells. Furtherexperiments were performed in mice to see if the ART treatment causedthe immune system to erroneously attack the host instead of diseaseagents. It did not.
Significance of the Mayo Clinic Research
The findings are significant because they suggest new ways touse an existing and approved drug regimen of ART to stimulate thethymus to produce more T cells -- without provoking an "autoimmune"reaction in which the body attacks itself. T cells are major diseasefighters of the immune system that are depleted in diseases such asAIDS and cancers, as well as in bone marrow transplant recipients. ARTis a combination treatment of antiretroviral drugs and drugs thatprevent cell death.
"One of the potential uses we envision is to use the ARTtreatment as a way to use tumor components to immunize cancer patientsagainst their own cancer cells," explains Mayo Clinic immunologistDavid McKean, Ph.D. "The current problem with this treatment strategyis that the tumor gives off a variety of soluble products which wedon't fully understand, but which we know wreck havoc on the immunesystem by suppressing its various components. If we can use the ARTdrugs to increase the number of newly produced T cells in cancerpatients first, we can potentially improve the likelihood of getting acancer vaccine to work."
The findings may also benefit the aging population.
"The ability of ART to boost T cell numbers may allow patientswho normally don't respond to vaccines -- such as those with chronicdisease, or the elderly -- to mount an effective immune response ifthey receive the vaccination in combination with ART," says co-authorand Mayo Clinic immunologist Andrew Badley, M.D.
With age the thymus (located in the upper chest) diminishes andproduces fewer T cells. This leaves the elderly more vulnerable todisease and less able to make effective use of vaccines. However,researchers say if the aging immune system was primed by the ARTregimen prior to receiving vaccines, a stronger immune response mightbe provoked. That way people might be better protected, and publichealth officials could use their supplies of vaccine more effectively.
About the Investigation
In the seven participants treated with ART, five showed adramatic 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 destroytumor cells or cells that have been infected by viruses to which theindividual has not been previously exposed. Says Dr. McKean, "A personin their 60s doesn't produce many new T cells. Yet in order toeffectively respond to a pathogen you haven't seen before, you reallyneed those new T cells produced by the thymus. So that's why as peopleget older they become more susceptible to particular viruses."
Collaboration and Support
In addition to Drs. McKean and Badley, the Mayo Clinic researchteam included Daniel Graham, Ph.D.; Michael P. Bell; Catherine Huntoon;Joel Weaver; and Nanci Hawley. Their work was supported by grants fromthe National Institutes of Health and the Burroughs WellcomeTranslational Research Award.
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