J Immunol. 2025 Oct 29:vkaf291. doi: 10.1093/jimmun/vkaf291. Online ahead of print.

ABSTRACT

The establishment of memory T cell responses is critical to protection against pathogens and is influenced by the conditions under which memory formation occurs. Iron is an essential micronutrient for multiple immunologic processes and nutritional deficiency is a common problem worldwide. Despite its prevalence, the impact of nutritional iron deficiency on the establishment of memory T cell responses is poorly understood. In this study we investigate the impact of nutritional iron deficiency on the generation, phenotype, and function of memory T cell responses using a murine model of dietary iron modulation in the context of influenza infection. Iron deficient mice have decreased systemic iron levels and develop significant anemia. Increased T cell expression of the transferrin receptor (CD71) is seen in iron deficient mice at baseline. During primary influenza infection, iron deficient mice experience increased weight loss but mount antigen specific T cells responses. Following recovery from infection, influenza specific memory T cells formed under iron deficient conditions are functionally impaired, most notably within the lung. Importantly, the ability to produce interferon γ (IFN-γ) and tumor necrosis factor α (TNF-α) remains impaired in CD8+ T cells despite co-culture with iron replete dendritic cells. These results establish a critical effect of nutritional iron deficiency on T cell memory development and function.

PMID:41159949 | DOI:10.1093/jimmun/vkaf291