The transforming growth factor beta signaling pathway is critical for the formation of CD4 T follicular helper cells and isotype-switched antibody responses in the lung mucosa

摘要

The influenza virus is thought to cause illness in up to 10% of adults and 30% of children each year worldwide. Most of these cases resolve on their own and don’t require treatment, but three to five million people are hospitalized and up to half a million people die each year. Unfortunately, the vaccines currently available to protect against influenza only target particular varieties or “strains” of the virus. The strains that circulate vary from year-to-year so it is necessary to develop new influenza vaccines every year. However, it is difficult to correctly predict which strains will circulate, so a more effective solution would be to develop a new vaccine that can help the body defend itself against many, or ideally any influenza strain. During a viral infection, a type of immune cell in the host can specialize into two different types of cells to help fight the virus T helper 1 cells and CD4 T follicular helper cells. T helper 1 cells help to kill host cells that have become infected. CD4 T follicular helper cells promote the production of proteins called antibodies, which identify and neutralize the virus. Here, Marshall et al. studied how T helper 1 cells and CD4 T follicular helper cells form in mice suffering from a lung infection similar to influenza. It was already known that a protein called transforming growth factor beta (TGF-β) helps the immune response to mount an effective defense against an infection without causing too much harm to the host. Marshall et al. show that TGF-β increases the number of CD4 T follicular helper cells in the mice by suppressing the production of another protein—called IL-2—on the surface of CD4 T cells. Treating mice lacking the ability to detect TGF-β with a drug that blocks a protein controlled by IL-2 also allows more CD4 T follicular helper cells to be produced. Marshall et al.’s findings reveal that TGF-β is involved in controlling the balance of T helper 1 cells and CD4 T follicular helper cells produced during viral infections of the respiratory tract. Since TGF-β also has other roles in immune responses against viruses, it is now an attractive target for the development of a vaccine that may protect us against all strains of the influenza virus.