Furthermore, the absence of INF-γ-producing Tfh cells, and therefore fewer lung-BRMs, was shown to compromise immune protection when mice were later reinfected with a different strain of influenza. Ballesteros-Tato and colleagues found that mice whose Tfh cells were unable to produce INF-γ had a dramatically reduced frequency and number of influenza-specific BRMs in the lungs. The production of INF-γ by Tfh cells turned out to be key to the lung-BRM response in flu. By Day 10, early in the flu infection, nearly 40 percent of the Tfh cells were producing interferon-gamma, or INF-γ but that frequency dropped sharply thereafter. They found that the number of Tfh cells increased quickly and peaked between days 10 and 15. The UAB researchers found that the preferential differentiation of lung-BRMs early after infection correlated with differences in the Tfh cell response early in the viral infection. Thus, Tfh cell help is required for class-switched-specific BRM responses to influenza. However, the UAB researchers found that, if mice were deficient in Tfh cells, or if the Tfh cells were blocked by an antibody, the lung-BRMs did not accumulate. Class-switched memory B cells that are primed against the influenza virus begin to appear in the lungs at day 10 of the infection, and their numbers peak at Day 30. Ballesteros-Tato is an associate professor in the UAB Department of Medicine Division of Clinical Immunology and Rheumatology.ĭuring influenza infection, both Tfh and B cells are present at germinal centers in the lymph nodes that drain the lungs. Also, there is need for vaccines that are more effective against later variants of a particular virus.Īndré Ballesteros-Tato, Ph.D., and colleagues at the University of Alabama at Birmingham have now published a mouse-model study in the journal Immunity showing that interferon-gamma produced by T follicular helper cells, or Tfh cells, after intranasal influenza infection is required to initiate the path of B cell differentiation into lung-BRMs. Yet flu vaccines are less effective in the elderly - the most at-risk population - compared to younger people. Seasonal influenza kills 290,000 to 650,000 people each year, according to the World Health Organization. Understanding the mechanism that creates these lung-BRMs is important for better flu vaccine development. They reside there permanently and lie in wait as the first layer of defense that can quickly react to produce antibodies in a future infection. Unlike antibody-producing B cells that help fight the current infection, the long-lived, non-circulating lung-BRMs migrate to the lungs from draining lymph nodes.
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