Gamma Delta Cells Potentially Play a Critical Role in Protecting Infants From Influenza Complications

Infants are a vulnerable population for influenza infections and are more likely to suffer complications such as hospitalization and even death from subsequent infections.

Research from a new study led by investigators from St. Jude Children’s Research Hospital, which appears in the journal Immunity, reported that gamma delta (γδ) T cells play a key role in protecting infants from flu complications.

These cells develop before birth and have the capability to respond rapidly to a wide range of infectious agents. The cells are concentrated in the cells lining the lungs along with other barrier tissues.

Although previous research has suggested that γδ T cells did not play a significant role in flu infections—particularly in adults—the investigators set out to explore whether or not γδ T cells do play a role in infant flu infections because the cells develop in utero and could potentially help protect the body during the period when the T cells are developing.

“We should consider modulation of γδ T cells and the lung repair pathway in neonates and infants as a therapeutic modality,” Paul Thomas, PhD, associate member of the Immunology Department at St. Jude Children’s Research Hospital and lead author of the study told Contagion®. “There are several companies starting to look at γδ T cells as therapeutic targets and our data indicate that their effects might be beneficial and also need to be considered in the context of particular ages.”

The investigators found that γδ T cells accumulated in response to flu infection in 7-day-old mice and also produced increased amounts of cytokine, interleukin-17A (IL-17A). In turn, increased IL-17A led to increased production of another signaling protein, the cytokine interleukin-33 (IL-33) in cells lining the lungs. IL-33 advances other immune cells, which produce the growth factor amphiregulin, which, in turn, promotes cell repair.

To confirm the role of IL-17A produced by the cells, the investigators performed a cell transfer experiment in wild-type or IL-17A deficient mice.

The investigators found that the loss of γδ T cells did not affect the ability of mice to eliminate the flu virus or to produce interferon-γ, a cytokine that promotes inflammation. However, a substantial difference in death rates between the 2 populations were observed. Death rates were higher in the mice without the γδ T cells that produced IL-17A or the gene for IL-33.

Investigators also found evidence of the same system at work in children <8 years. An analysis of nasal fluid from 25 infants with confirmed flu infections revealed that IL-17A, IL-33, and amphiregulin levels were correlated. Children and infants with mild disease outcomes had significantly higher levels of IL-17A than those with severe outcomes.

“These data indicate that the novel IL-17A-IL-33-Areg axis may serve as a potential therapeutic target during infant influenza infection,” the authors write.

Future studies are needed to verify the importance of the axis and to learn more about the function of the γδ T cells in humans. “We have ongoing studies in diverse infections and populations, with a particular focus on infants and young children,” Dr. Thomas told Contagion®.