Oct. 11, 2004 PHILADELPHIA -- Researchers at the University of Pennsylvania have discovered a "central memory" form of "helper" T cells that can offer immunity to leishmaniasis, a disease that causes considerable death and disfigurement across the globe and has been found in U.S. military personnel returning from Afghanistan and Iraq.
In the October issue of Nature Medicine, the Penn researchers describe how the discovery can offer immunity to leishmaniasis, even without the persistent presence of the parasite that caused the disease. Their findings encourage a new approach to creating a vaccine against leishmaniasis and other immune cell mediated diseases such as tuberculosis and HIV/AIDS.
Attempts to create a vaccine for leishmaniasis have long been stymied by the fact that the helper T cells, which coordinate the immune response against a pathogen, need constant stimulation from the pathogen in order to remain effective against the disease.
"Without the persistent attack from the Leishmania parasite, the immune system does not keep protective CD4+ T cells in place," said Phillip Scott, professor and chair of the Department of Pathobiology at Penn's School of Veterinary Medicine. "The strategy of most vaccines, to 'teach' the immune system to remember a pathogen, just doesn work with leishmaniasis.
"We have found that a new form of long-term memory T cell will, if stimulated, turn into the sort of helper T cells that mediate the immune response. We believe that, if we can stimulate the expansion of these central memory T cells, we ought to be able to create an effective vaccine."
Leishmaniasis is a parasitic disease spread by the bite of sand flies infected with the protozoan Leishmania. While the disease is most common in North Africa, the Middle East and Asia, it has been recently been seen in United States military personnel who have served in Afghanistan and Iraq.
According to the Centers for Disease Control, each year the world sees 1.5 million new cases of cutaneous leishmaniasis, which infects the skin, causing scarring boils, and 500,000 new cases of visceral leishmaniasis, which infects internal organs, causing death if left untreated.
Particularly vexing to researchers has been the fact that while people who recover from leishmaniasis generally develop lifelong immunity to reinfection, this has been thought to depend upon the continued presence of the Leishmania parasite. Indeed, it has been shown in mice that if the parasite is entirely removed, the host can become reinfected with disease.
Scott and his colleagues wondered if, despite the apparent loss of immunity when the parasites disappeared, there were any T cells that still retained memory of Leishmania. Recent studies have shown that memory T cells may be of more than one type. One type, which is less activated and found in the lymph nodes, is called central memory T cells. Since little is known about CD4+ T cell memory during chronic disease, the Penn researchers set out to find if such central memory cells exist in leishmaniasis.
The hunt for the theoretical CD4+ central memory T cells began by transferring T cells from mice infected with leishmaniasis to mice who had never faced the disease. According to Scott, some of the transferred T cells went to the lymph nodes, and had the characteristics of central memory cells.
"We see that these central memory T cells but not the effector T cells persist in the absence of obvious parasites for as long as five months," Scott said. "Since we still do not know much about these new T cells, our next step is to find out how we can encourage the proliferation of central memory cells and stimulate them to fight disease."
According to Scott, a better understanding of central memory T cells may lead to the development of vaccines that fight off a range of pathogens that respond well to a helper T cell response.
Funding for this research was provided through grants from the National Institutes of Health.
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