Helper T cell differentiation
Open accessAbstract
CD4+ T helper cells are key regulators of host health and disease. In the original model, specialized subsets of T helper cells are generated following activation through lineage-specifying cytokines and transcriptional programs, but recent studies have revealed increasing complexities for CD4+ T-cell differentiation. Here, we first discuss CD4+ T-cell differentiation from a historical perspective by highlighting the major studies that defined the distinct subsets of T helper cells. We next describe the mechanisms underlying CD4+ T-cell differentiation, including cytokine-induced signaling and transcriptional networks. We then review current and emerging topics of differentiation, including the plasticity and heterogeneity of T cells, the tissue-specific effects, and the influence of cellular metabolism on cell fate decisions. Importantly, recent advances in cutting-edge approaches, especially systems biology tools, have contributed to new concepts and mechanisms underlying T-cell differentiation and will likely continue to advance this important research area of adaptive immunity.
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The current view is that CD4 Th cell subsets are not separate lineages but have plasticity and form a continuum of mixed functional capacities.
“However, the current view is that CD4 Th cell subsets are not separate lineages but have plasticity and form a continuum of mixed functional capacities [177, 178].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [178]
The Introduction (page not provided) describes plasticity: differentiated CD4+ T cells can adopt alternative expression profiles and produce cytokines associated with other subsets. It also describes a continuum of developmental states and a spectrum of functional states in TH17 cells. It does not establish the broader assertion that CD4+ T helper subsets are not separate lineages at all. (LLM, conf=0.86)
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Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)
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- Authors
- Saravia, J., Chapman, N. M., & Chi, H.
- Affiliations
- St. Jude Children's Research Hospital (US)
- Corresponding author
- Chi, Hongbo
- Venue
- Cellular & Molecular Immunology
- Published
- 2019-03-12
- Volume
- 16
- Issue
- 7
- Pages
- 634-643
- ISSN
- 1672-7681 (ISSN-L)
- 2042-0226
- PMC
- PMC6804569
- OpenAlex
- W2921191661
- Cited by
- 489
- References
- 218
- Citations by year
- 2026: 33 · 2025: 85 · 2024: 114 · 2023: 94 · 2022: 80 · 2021: 44 · 2020: 34 · 2019: 5
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cellular and Molecular Immunology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Foundation for the National Institutes of Health
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- CD4+ T helper cells, T helper cell differentiation, T helper cell subsets, transcriptional regulatory networks, T cell plasticity, T cell heterogeneity, cellular metabolism, cell fate determination, systems biology
- MeSH terms
- Animals, Cell Differentiation, T-Lymphocytes, Helper-Inducer, Humans, Cytokines, Cell Lineage, Gene Regulatory Networks, Adaptive Immunity
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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