New origin found for a critical immune response

cao1976

原贴由Rojjer发表于 2009-3-11 14:00
http://biosky.haotui.com/thread-8438-1-9.html

An immune system response that is critical to the first stages of fighting off viruses and harmful bacteria comes from an entirely different direction than most scientists had thought, according to a finding by researchers at the Duke University Medical Center. "This finding will have important implications in vaccine science and autoimmune disease therapy development," said Michael Gunn, M.D., an immunologist and cardiologist at Duke and senior author of the study published in Nature Immunology.

Type 1 helper (TH1) T cell immune responses are critical for the control of viruses and certain bacteria. Immunologists have generally believed that TH1 responses are induced by rare immune cells, called dendritic cells. When activated by infection or vaccination, the dendritic cells were thought to move from peripheral tissues into lymph nodes to stimulate T cell responses.

The Duke researchers found, however, that the dendritic cells that stimulate TH1 responses didn't come from peripheral tissues, but rather arose from monocytes, a common cell type in the blood, that moved directly into lymph nodes after infection.

"The result speaks to the most basic principles of immune response to pathogens," Gunn said. "It may also explain the poor results we have seen in attempts to develop effective dendritic-cell vaccines."

Gunn previously had identified a particular protein, known as a chemokine, that stimulates the migration of activated dendritic cells from peripheral tissues to lymph nodes. The Duke 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."

One scientist who knew about these findings told Gunn the Duke group would "never figure this out" because their findings were so unconventional.

To solve the mystery, the Duke team studied several different types of mice, which were missing other chemokines or chemokine receptors. They found that mice without the Ccr2 chemokine receptor that controls the migration of inflammatory monocytes had much lower accumulation of monocyte-derived dendritic cells and TH1 responses.

The scientists concluded 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," Gunn said. "We found out that that's not always the case."

The team now plans to look at the blood-derived dendritic cells under different conditions to see if they may have other activities. "We observed the activity of these cells after TH1-inducing stimuli, like influenza," Gunn said. "Next we'd like to study other types of immune stimuli to see how the cells respond."

Understanding how dendritic cells stimulate different types of immune response would open the door to enhancing or inhibiting these responses, a major goal of immunologists trying to prevent infections or control autoimmune disease, Gunn said.

Source: Duke University Medical Center

杜克大学医学院免疫学系，NIH呼吸生物学研究实验室等处的研究人员在Nature Immunology上发表免疫学的新成果。



当机体面对外界入侵的有害细菌和病毒时，免疫应答是机体应对入侵的关键第一步。杜克大学新的研究成果将为疫苗设计和自体免疫疾病的研究带来新的启示。领导这一研究的是杜克大学医学院的免疫学和心脏学专家Michael Gunn。



经典的免疫学理论认为，1型辅助T细胞应答是病毒免疫和细菌免疫的关键所在，免疫学家相信，TH1（1型辅助T细胞）应答能被少数的免疫细胞激活，这种少数的细胞被称为树突细胞。当免疫系统被感染或是疫苗激活时，树突细胞从周围组织迁徙到淋巴结激活T细胞产生应答。



但是杜克大学的研究者发现，激活T细胞不是来自周围组织的树突细胞，而是来自血液中的单核细胞，在感染发生后其从血液中直接赶去感染部位激活TH1引发免疫应答。这一结果改写了经典的免疫学理论，这也解释了为何我们研发树突细胞疫苗总失败。



Michael发现，感染发生后血液中的炎症单核细胞会转变为CD11C+11bhiGr-1+炎性树突细胞，并集结移动进入淋巴结，激活TH1细胞。在这一过程中需要趋化因子受体CCR2参与。



这一研究结果表明血液中炎性单核细胞衍生的树突细胞在TH1免疫应答过程中起关键的激活作用，Michael下一步将研究不同条件下血液衍生的树突细胞对免疫系统的激活情况，这些成果也许对自体免疫疾病和疫苗研究有更佳的指导作用。