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Smrithi S. Menon, Aisha Souquette, E Kaitlynn Allen, Deryn St. James, Robert Mettelman, Brandi Clark, Jeremy Chase Crawford, Tanya Novak, Adrienne Randolph, Paul Thomas, T cell responses in pediatric patients with severe influenza disease., The Journal of Immunology, Volume 212, Issue 1_Supplement, May 2024, Page 0581_4574, https://doi.org/10.4049/jimmunol.212.supp.0581.4574
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Abstract
Influenza virus infections impose a high risk of disease-related complications in children leading to hospitalization, and increased mortality. However, it is still unclear why only some children become critically ill. The Pediatric Intensive Care Influenza 2 study enrolled children and young adults with influenza-related critical illness, aiming to identify predictive and prognostic biomarkers of severe disease (SD). To this end, we characterized T cell populations and functional responses to influenza, to understand how adaptive immunity fails to protect patients in this cohort from SD. Our preliminary studies indicate an increased level of ICOS expressing circulating T follicular helper cells (cTfh) in patients with SD while an elevation in the levels of effector memory CD4 and CD8 T cell populations in patients with moderate disease. Moreover, an enhanced level of IL21, CXCR3, ICOS and PD1 producing cTfH cells was observed in SD patients within the age group of 9-19 yrs. Age dependent varying expression of IL2, granzyme B producing CD4 T cells, CXCR3, ICOS producing and IL21 expressing cTfH cells was also observed. Additional T cell characterization is underway to integrate the influence of patient parameters such as vaccination status. T cell repertoire profiling and assessment of epitope-specific T cell populations using single-cell sequencing is being conducted to understand how pre-existing anti-influenza immunity affects disease severity and outcome.
