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Aging restricts maturation of CXCL13+ T follicular helper cells in human immunity

ABSTRACT: Secondary lymphoid organs are concentrated sites of adaptive immune responses, but how these structures change over the lifespan is unclear. Recent work has revealed unique alterations to T follicular helper (Tfh) cells in older individuals. However, the gene-regulatory control of Tfh cell development in the context of aging has not been explored. Here, we characterized Tfh cells from human tonsil tissue, finding impaired B cell help, reduced tissue organizational cues, and restricted development with age. Maturation of Tfh cells in older adults was limited by gene-expression programs acquired during early differentiation of naïve CD4T cell precursors, including targets of critical transcriptional regulators like TCF7 and LEF1. Collectively, these results suggest that the transcriptional control of naïve CD4T cell differentiation has a lasting impact on subsequent Tfh maturation. Therefore, the state of the naïve CD4T cell pool during human aging can impair the ability to mount a protective adaptive immune response.

ORGANISM(S): Homo sapiens

PROVIDER: GSE270554 | GEO | 2026/04/27

REPOSITORIES: GEO

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