Scientists find new origin for a critical immune response

March 2nd, 2009 - 12:57 pm ICT by ANI  

London, March 2 (ANI): Researchers at the Duke University Medical Center say that an immune system response, key to the first stages of fighting off viruses and harmful bacteria, has an entirely different origin than what has been thought to date.
“This finding will have important implications in vaccine science and autoimmune disease therapy development,” Nature magazine quoted said Dr. Michael Gunn, an immunologist and cardiologist at Duke, as saying.
It has been beliefved thus far that Type 1 helper (TH1) T cell immune responses, critical for the control of viruses and certain bacteria, are induced by rare immune cells, called dendritic cells.
Immunologists have generally believed that upon being activated by infection or vaccination, the dendritic cells move from peripheral tissues into lymph nodes to stimulate T cell responses.
However, the Duke researchers have discovered that the dendritic cells that stimulate TH1 responses do not come from peripheral tissues.
According to them, the dendritic cells rather arise from monocytes, a common cell type in the blood, which move directly into lymph nodes after infection.
“The result speaks to the most basic principles of immune response to pathogens. It may also explain the poor results we have seen in attempts to develop effective dendritic-cell vaccines,” Gunn said.
A previous study conducted by Gunn had led to the identification of a particular protein, known as a chemokine, that stimulates the migration of activated dendritic cells from peripheral tissues to lymph nodes.
In the current study, the researchers generated a TH1 response in laboratory mice that lacked this chemokine with influenza viruses.
“We really thought the mice would not be able to generate much of an immune response at all,” Gunn said, because they wouldn”t be able to mobilize dendritic cells.
“The mice, however, had increased TH1 responses. We knew we had to find what was really causing the response,” the researcher added.
Gunns team studied several different types of mice that were missing other chemokines or chemokine receptors, and found that the animals lacking the Ccr2 chemokine receptorwhich controls the migration of inflammatory monocyteshad much lower accumulation of monocyte-derived dendritic cells and TH1 responses.
Based on their observations, the researchers came to the conclusion that there is a blood-derived lymph node dendritic cell type that has a key role in developing acute T-cell responses.
“For so long, dendritic cells from tissues were the obvious answer. We found out that that’’s not always the case,” Gunn said.
The Duke researchers are now planning to study the blood-derived dendritic cells under different conditions, in order to determine whether they may have other activities.
“We observed the activity of these cells after TH1-inducing stimuli, like influenza. Next we”d like to study other types of immune stimuli to see how the cells respond,” Gunn said.
The researchers believes that understanding how dendritic cells stimulate different types of immune response might open the door to enhancing or inhibiting such responses, a major goal of immunologists trying to prevent infections or control autoimmune disease, Gunn said.
The study has been published in the journal Nature Immunology. (ANI)

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