@article{5086,
  keywords = {Autoimmunity, Immune tolerance},
  author = {Xin Chen and Mustafa Ghanizada and Vamsee Mallajosyula and Elsa Sola and Robson Capasso and Karan Raj Kathuria and Mark M. Davis},
  title = {Differential roles of human CD4+ and CD8+ regulatory T cells in controlling self-reactive immune responses},
  abstract = {Here we analyzed the relative contributions of CD4+ regulatory T cells expressing Forkhead box protein P3 (FOXP3) and CD8+ regulatory T cells expressing killer cell immunoglobulin-like receptors to the control of autoreactive T and B lymphocytes in human tonsil-derived immune organoids. FOXP3 and GZMB respectively encode proteins FOXP3 and granzyme B, which are critical to the suppressive functions of CD4+ and CD8+ regulatory T cells. Using CRISPR–Cas9 gene editing, we were able to achieve a reduction of ~90–95% in the expression of these genes. FOXP3 knockout in tonsil T cells led to production of antibodies against a variety of autoantigens and increased the affinity of influenza-specific antibodies. By contrast, GZMB knockout resulted in an increase in follicular helper T cells, consistent with the ablation of CD8+ regulatory T cells observed in mouse models, and a marked expansion of autoreactive CD8+ and CD4+ T cells. These findings highlight the distinct yet complementary roles of CD8+ and CD4+ regulatory T cells in regulating cellular and humoral responses to prevent autoimmunity.},
  year = {2025},
  journal = {Nature Immunology},
  pages = {1-10},
  month = {2025-01-13},
  issn = {1529-2916},
  url = {https://www.nature.com/articles/s41590-024-02062-x},
  doi = {10.1038/s41590-024-02062-x},
  language = {en},
}