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Chemical guidance of T cells leads to immunologic memory and long-term immunity

In the latest issue of the journal Nature, scientists at the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) describe a new understanding about how long-term immunity works--findings that may lead to new ways of thinking about how to enhance certain immune responses and how to improve vaccines.

Led by immunologist Ronald Germain, M.D., Ph.D., the scientists took videos through a microscope to document what happens inside the lymph nodes of a living mouse shortly after a vaccination. The videos reveal that the movement of a specific type of immune cell known as a CD8+ T cell, also called a cytotoxic T cell, is not random as was previously thought, but instead is guided by chemical signals released from other cells.

Scientists have long recognized the importance of understanding how CD8+ T cells move through the lymph nodes and become activated. Once active, CD8+ T cells roam throughout the body destroying cells infected with bacteria or viruses--a process known as cell-mediated immunity. When these CD8+ T cells encounter an infected cell, they unleash a torrent of substances that poke holes in the cell's membrane, chew up its proteins and ultimately cause it to die. They also produce molecules such as interferon-gamma that help activate other immune cells.

After they fight the initial infection, some of these CD8+ T cells remain in the circulation as memory cells, primed to fight if the host is re-infected with the same pathogen. Memory cells are key to vaccine strategies being studied for infectious agents such as HIV. But the CD8+ T cells can only become effective, long-lived memory cells after they encounter certain other cells in the lymph node that can activate them.

The new research, conducted largely by senior postdoctoral fellows Flora Castellino, M.D., and Alex Huang, M.D., Ph.D., with Dr. Germain's guidance, shows that when CD8+ T cells enter the lymph node, a
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Contact: Jason Socrates Bardi
jbardi@niaid.nih.gov
301-402-1663
NIH/National Institute of Allergy and Infectious Diseases
17-Apr-2006


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