Research ArticleT CELLS

Developmental bifurcation of human T follicular regulatory cells

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Science Immunology  28 May 2021:
Vol. 6, Issue 59, eabd8411
DOI: 10.1126/sciimmunol.abd8411

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Reconstructing TFR cell development

Antibody responses, including against self-antigens, are tightly controlled within germinal centers (GCs) by balancing the activity of T follicular regulatory (TFR) and helper (TFH) cells. Kumar et al. reconstructed the developmental trajectory of TFR cells using flow cytometry indexed single-cell transcriptomics of follicular T cells isolated from human peripheral blood, lymph nodes, and tonsils. After distinguishing TFR cells from other follicular T cell populations based on gene signature, they used transcriptomics to support a model in which mature GC TFR cells arise from regulatory T cells, with circulating TFR cells representing a separate developmental pathway. These results suggest that mature TFR cells primarily arise independently from their less mature counterpart in peripheral blood, providing further insight into how human TFR cells develop.

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