Acquisition of lymphokine-producing phenotype by CD4+ T cells
Abstract
Naive CD4+ T cells when stimulated produce IL-2 as their major lymphokine. Upon priming, these cells develop into cells that produce either IFN gamma, TNF beta, and IL-2 or IL-4 and its congeners. The former cells are designated TH1-like, and the latter TH2-like. Here we review the regulation of the differentiation of naive CD4 cells into IFN gamma- or IL-4-producers. The dominant factors that determine such differentiation are lymphokines and other cytokines. IL-2 itself appears to be required for naive cells to develop into TH1- or TH2-like cells but is not deterministic of their differentiation fate. If IL-4 is also present during the priming period, the resultant CD4+ T cells produce IL-4 upon restimulation; the development of IFN gamma-producing cells is strikingly inhibited by IL-4. In the absence of IL-4, priming for IFN gamma-production occurs, but this is markedly enhanced by IL-12. The role of IFN gamma in enhancing priming for IFN gamma-production is not fully resolved. In some in vitro systems, it appears to act together with IL-12 to enhance such production. Anti-IFN gamma diminishes priming for IFN gamma production in vivo. Lymphokines also exert a "cross-regulatory" or inhibitory effect. As noted above, IL-4 strikingly diminishes priming for IFN gamma production, although this inhibitory effect is blunted in the presence of IL-12. IFN gamma similarly diminishes priming for IL-4 production; this effect is principally observed when low concentrations of IL-4 are used in the priming culture. Although other factors may play a role in the determination of lymphokine-producing phenotype, such as antigen dose, type of antigen-presenting cell, and expression of accessory molecules and hormones, these effects appear to be secondary to the dominant role of the lymphokines and cytokines.
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TH1 cells produce IFN-γ, TNF, IL-2, GM-CSF and related cytokines which stimulate macrophages and neutrophils to kill intracellular but also extracellular bacteria.
“T H 1 cells produce IFN-γ, TNF, IL-2, GM-CSF and related cytokines which stimulate macrophages and neutrophils to kill intracellular but also extracellular bacteria (Seder and Paul, 1994;Weiss and Schaible, 2015).”
From Iron in infection and immunity (2020) · cites this paper as Seder and Paul, 1994
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- Authors
- Seder, R. A., & Paul, W. E.
- Affiliations
- National Institutes of Health (US)
- ORCID
- Seder, R A
- Venue
- Annual Review of Immunology
- Publisher
- Annual Reviews
- Published
- 1994-04
- Volume
- 12
- Issue
- 1
- Pages
- 635-673
- ISSN
- 0732-0582 (ISSN-L)
- 1545-3278
- OpenAlex
- W2037061225
- Cited by
- 1,557
- References
- 0
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 10 · 2023: 5 · 2022: 9 · 2021: 10 · 2020: 14 · 2019: 13 · 2018: 9 · 2017: 11 · 2016: 12 · 2015: 17 · 2014: 33 · 2013: 22 · 2012: 27
- FWCI
- 41.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Immunology (publishedVersion)
- PubMed (publishedVersion)
- 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 › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- CD4+ T cell differentiation, Th1 cells, Th2 cells, interleukin-2, IL-4, interferon-gamma, IL-12, naive T cell priming, T cell activation
- MeSH terms
- Animals, Antigen-Presenting Cells, T-Lymphocytes, Helper-Inducer, Humans, Interferon-gamma, Interleukins, Lymphocyte Activation, Lymphokines, Tumor Necrosis Factor-alpha, CD4-Positive T-Lymphocytes
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