ArticleNature immunology2022
Reversal of the T cell immune system reveals the molecular basis for T cell lineage fate determination in the thymus.
Article in Nature immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 43 citations in OpenAlex.
- Generation of effector CD4Stem cell reports · 2026Article
- Perp Deficiency Induces Defective Negative Selection and Autoimmune Arthritis in Aged Mice.Aging cell · 2026Article
- Unraveling CD8 lineage decisions reveals that functionally distinct CD8Nature immunology · 2026Article
- Solving the puzzle of CD8 T cell positive selection.Nature immunology · 2026Article
- UBL3 Participates in the Early Stages of CD83-Dependent CD4European journal of immunology · 2026Article
- Single-cell transcriptome delineating asymmetric dynamics of CD4Frontiers in immunology · 2026Article
- Development of αβ and γδ T Cells in the Thymus and Methods of Analysis.International journal of molecular sciences · 2025Review
- Preselection CD4bioRxiv : the preprint server for biology · 2025Article
- Cytotoxic T Cells: Kill, Memorize, and Mask to Maintain Immune Homeostasis.International journal of molecular sciences · 2025Review
- T Cell Development: From T-Lineage Specification to Intrathymic Maturation.Advances in experimental medicine and biology · 2025Review
- Adjusting to self in the thymus: CD4 versus CD8 lineage commitment and regulatory T cell development.The Journal of experimental medicine · 2024Review
- The partitioning of TCR repertoires by thymic selection.The Journal of experimental medicine · 2024Review
- Heterogeneity of lymphocyte subsets in predicting immune checkpoint inhibitor treatment response in advanced lung cancer: an analysis across different pathological types, therapeutic drugs, and age groups.Translational lung cancer research · 2024Article
- PACSIN1 promotes immunosuppression in gastric cancer by degrading MHC-I.Acta biochimica et biophysica Sinica · 2024Article
- Helper T cell immunity in humans with inherited CD4 deficiency.The Journal of experimental medicine · 2024Article
- Pathways and mechanisms of CD4Trends in immunology · 2024Review
- Integrative temporal multi-omics reveals uncoupling of transcriptome and proteome during human T cell activation.NPJ systems biology and applications · 2024Article
- New insights into developmental fate decisions by autoreactive CD4 thymocytes.Clinical and translational medicine · 2024Article
- A guide to thymic selection of T cells.Nature reviews. Immunology · 2024Review
- S1PR1 mediates Th17 cell migration from the thymus to the skin in health and disease.Frontiers in immunology · 2024Article
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12 authors at 2 institutions in 2 countries.
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Abstract
T cell specificity and function are linked during development, as MHC-II-specific TCR signals generate CD4 helper T cells and MHC-I-specific TCR signals generate CD8 cytotoxic T cells, but the basis remains uncertain. We now report that switching coreceptor proteins encoded by Cd4 and Cd8 gene loci functionally reverses the T cell immune system, generating CD4 cytotoxic and CD8 helper T cells. Such functional reversal reveals that coreceptor proteins promote the helper-lineage fate when encoded by Cd4, but promote the cytotoxic-lineage fate when encoded in Cd8-regardless of the coreceptor proteins each locus encodes. Thus, T cell lineage fate is determined by cis-regulatory elements in coreceptor gene loci and is not determined by the coreceptor proteins they encode, invalidating coreceptor signal strength as the basis of lineage fate determination. Moreover, we consider that evolution selected the particular coreceptor proteins that Cd4 and Cd8 gene loci encode to avoid generating functionally reversed T cells because they fail to promote protective immunity against environmental pathogens.
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