A scientific discovery by Fox Chase Cancer Center researchers helps explain how "memory" T cells protect the body from viral diseases. The research published today in Proceedings of the National Academy of Science Online Early Edition shows lymph nodes are not just organs where immune cells reside and proliferate, but also are the sites where a major fight against the spread of an invading virus occurs.
After becoming sick from many viruses, the body becomes "immune" (protected) from recurrence of the same disease. This is why before vaccines were developed, childhood diseases such as measles and mumps occurred only once in a lifetime. The immunity occurs when the immune system produces cells called lymphocytes that specifically attack and eliminate the virus at the time of infection. After the infection subsides, most of the lymphocytes die but some remain in the body as "memory lymphocytes" and protect the body from recurrence of the disease. Similarly, vaccines induce the production of memory lymphocytes, but without causing disease.
While scientists have long known the role of antibodies in protection, whether memory cells, known as CD8 T cells, could prevent viral diseases has been debated. The new work by Fox Chase virologist Luis J. Sigal, D.V.M., Ph.D., and his Fox Chase colleagues in the virology and pathology programs, provides the basis whereby memory CD8 T cells do, in fact, prevent viral diseases.
CD8 T cells normally reside in lymphoid organs such as the lymph nodes. It was thought that to protect from disease, memory CD8 T cells needed first to multiply in the lymph nodes and then migrate through the blood to kill infected cells at the site where the virus entered the body (most commonly the skin, the lungs or the gut). This process of lymphocyte multiplication and migration may take several days while viruses multiply and spread quicker. Sigal's work shows the CD8 T cells can protect from viral disease without the need to migrate from the lymph nodes to the site of viral entry.
"It was very difficult to imagine how the memory T cells could win this race," said Sigal, the lead author of the study.
The Fox Chase experiments show that memory CD8 T cells rapidly multiply and kill target cells inside the lymph node.
"In fact we found that memory CD8 T cells already killed target cells in the lymph node and decreased viral spread to the liver and spleen when the virus just barely started to multiply."
Thus, memory CD8 T cells do not prevent infection; but prevent disease partly because they curb the spread of the virus from the lymph node to vital organs at very early stages of the infection.
"It's like having a security check point," said Sigal. "Also, many cancers, like viruses, must pass through lymph nodes to metastasize, so this research may help develop vaccines that prevent tumor metastases."
Sigal's co-authors include postdoctoral associates Ren-Huan Xu, Ph.D. and Min Fang, Ph.D.; and senior member Andres Klein-Szanto, M.D., all of Fox Chase Cancer Center. This research was supported by three grants from the National Institutes of Health, along with an appropriation from the Commonwealth of Pennsylvania to Fox Chase Cancer Center. Fox Chase Cancer Center was founded in 1904 in Philadelphia as the nation's first cancer hospital. In 1974, Fox Chase became one of the first institutions designated as a National Cancer Institute Comprehensive Cancer Center. Fox Chase conducts basic, clinical, population and translational research; programs of cancer prevention, detection and treatment of cancer; and community outreach. For more information about Fox Chase activities, visit the Center's web site at www.fccc.edu or call 1-888-FOX CHASE.