Internal Medicine Research

Dynamics of CD4+ T Follicular Helper Cell Responses to Influenza Vaccination

Article Impact Level: HIGH
Data Quality: STRONG
Summary of Nature Immunology, 1–12. https://doi.org/10.1038/s41590-024-01926-6
Dr. Stefan A. Schattgen et al.

Points

  • The study observed a significant increase in circulating and lymph node TFH cells one week after influenza vaccination, with lymph node TFH cells maintaining elevated levels for at least three months.
  • Researchers identified multiple TFH cell subsets within lymph nodes, including pre-TFH, memory TFH, germinal center (GC) TFH, and interleukin-10+ TFH cells, present at baseline and after vaccination.
  • The transition to a GC TFH cell phenotype was faster following the second vaccination, indicating an enhanced immune response upon re-exposure to the influenza antigen.
  • The study found several influenza-specific TFH cell clonal lineages, demonstrating the immune system’s ability to effectively target internal influenza virus proteins.
  • The findings suggest that TFH cells form a durable and dynamic network across tissues, providing insights that could help optimize future vaccine strategies.

Summary

In a detailed study analyzing the differentiation and specificity of human CD4+ T follicular helper cells (TFH cells) following influenza vaccination, researchers tracked the evolution of TFH cell responses over two years in human volunteers. Blood and draining lymph node (LN) samples were collected after administering two influenza vaccines one year apart. Initial findings revealed a marked increase in the frequency of circulating TFH (cTFH) and LN TFH cells at one-week post-vaccination. This surge in cTFH cells was transient, while LN TFH cells continued to expand through the second week and sustained elevated levels for at least three months.

Further analysis identified diverse TFH cell subsets within the lymph nodes, including pre-TFH cells, memory TFH cells, germinal center (GC) TFH cells, and interleukin-10+ TFH cells, present from the baseline and across all post-vaccination time points. Notably, the transition towards a GC TFH cell phenotype occurred more rapidly after the second vaccination compared to the first. This observation suggests an enhanced immune system responsiveness upon re-exposure to the influenza antigen.

The study also uncovered several influenza-specific TFH cell clonal lineages, demonstrating the targeting of internal influenza virus proteins. Each TFH cell state, indicative of a robust immune response, was achievable within these clonal lineages. These results highlight the capacity of human TFH cells to form a durable and dynamic network across multiple tissue types, offering insights into their pivotal roles in vaccination-induced immunity and potential avenues for optimizing vaccine strategies.

Link to the article: https://www.nature.com/articles/s41590-024-01926-6

References

Schattgen, S. A., Turner, J. S., Ghonim, M. A., Crawford, J. C., Schmitz, A. J., Kim, H., Zhou, J. Q., Awad, W., Mettelman, R. C., Kim, W., McIntire, K. M., Haile, A., Klebert, M. K., Suessen, T., Middleton, W. D., Teefey, S. A., Presti, R. M., Ellebedy, A. H., & Thomas, P. G. (2024). Influenza vaccination stimulates maturation of the human T follicular helper cell response. Nature Immunology, 1–12. https://doi.org/10.1038/s41590-024-01926-6

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