May 17, 2002 Irvine, Calif., May 16, 2002 — White blood cells are much more active and dynamic than previously assumed and show complex behaviors for responding to foreign bodies, a University of California, Irvine study has shown for the first time.
The study also marks the first time researchers have seen single immune system cells operating in intact lymph nodes, their native environment in the body, and gives new insight into the tactics used by these cells, known as T- and B-cells, to fight disease. The researchers' study appears in the May 16 issue of Science Express, the online version of Science magazine.
Ian Parker, professor of neurobiology and behavior; Michael Cahalan, professor of physiology and biophysics; and Mark Miller, postgraduate researcher, adapted a technique called two-photon imaging to observe individual T-cells and B-cells in mice as the cells moved within lymph nodes in the body. The technique allowed the researchers to observe the cells' behavior in ways that had never been possible using previous techniques.
"Previously, researchers had not been able to see the behavior of these cells in their native immune organs. When looking at the cells' behavior, the lymph node had been a 'black box' with no direct information on how cells were interacting," Parker said. "This new form of microscopy gives us an unprecedented view of how the immune system functions. The cells are moving and changing shape in ways that we've never seen; this should provide insight on how disease is combated and perhaps even how the immune system can fail."
The researchers found that T- and B-cells move much faster in their native lymph nodes than seen in previous research and that the cells appear to move randomly when not stimulated by any number of chemical signals or foreign bodies. The researchers also noticed that T-cells abruptly changed their shape, speed and direction, suggesting that they were interacting with some unseen body or signal as they explored the environment within the lymph node.
T-cells, which are responsible for directing the body's immune response against foreign bodies (including pathogens) explored a much wider territory within the lymph node than did B-cells, which produce antibodies that help target foreign bodies for destruction.
The two-photon imaging system hooks up a pulsed laser with a light microscope. The ultra-fast laser pulses allow imaging of cells lying relatively deep within tissues (such as the lymph nodes in this study), and a computer generates three-dimensional pictures so researchers can review the cells' activity as it actually happens.
"The images are giving us a wealth of information on how these cells move about in their environment. Right now, we're like naturalists studying a new species in the wild," Cahalan said.
"These environmental interactions may be key to understanding how white cells function in a living animal and provide valuable insight for the development of new immunosuppressive drugs," Miller said. "We think this technique will also be useful for studying cells in other areas of the immune system, such as the thymus gland, spleen and even sites of inflammation and disease."
The researchers, who worked for two years to get the images used in this study, now are looking at using the two-photon technique in other parts of the body and to further determine the cellular interactions that occur in the immune system.
Parker, Miller and Cahalan's colleagues included Sindy Wei of UCI. Their research was supported by grants from the National Institute of Allergy and Infectious Disease and the National Institute of General Medical Sciences.
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