CD4 + T Cells: Differentiation and Functions

Luckheeram, Rishi Vishal; Zhou, Rui; Verma, Asha Devi; Xia, Bing

doi:10.1155/2012/925135

Cited by 1,381T-cell and B-cell ImmunologyPsoriasis: Treatment and PathogenesisCytokine Signaling Pathways and Interactions

CD4 + T Cells: Differentiation and Functions

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Luckheeram, Rishi Vishal, Zhou, Rui, Verma, Asha Devi, Xia, Bing·2012·Clinical and Developmental Immunology

DOI 10.1155/2012/925135PMC PMC3312336

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Abstract

CD4 + T cells are crucial in achieving a regulated effective immune response to pathogens. Naive CD4 + T cells are activated after interaction with antigen-MHC complex and differentiate into specific subtypes depending mainly on the cytokine milieu of the microenvironment. Besides the classical T-helper 1 and T-helper 2, other subsets have been identified, including T-helper 17, regulatory T cell, follicular helper T cell, and T-helper 9, each with a characteristic cytokine profile. For a particular phenotype to be differentiated, a set of cytokine signaling pathways coupled with activation of lineage-specific transcription factors and epigenetic modifications at appropriate genes are required. The effector functions of these cells are mediated by the cytokines secreted by the differentiated cells. This paper will focus on the cytokine-signaling and the network of transcription factors responsible for the differentiation of naive CD4 + T cells.

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CD4 Th cell subsets participate in a range of diverse and overlapping adaptive immune responses.
“CD4 Th cell subsets participate in a range of diverse and overlapping adaptive immune responses [179, 180].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [180]
Tfh cells are important for generating memory B cells, plasma cells, and antibodies, while Th1 cells help improve memory CD8+ T cell responses.
“CD4+ T follicular helper (Tfh) cells have key roles in the development of memory B cells, plasma cells, and antibodies, whereas Th1 cells support and enhance the quality of memory CD8+ T cell responses (Crotty, 2011; Krawczyk et al., 2007; Luckheeram et al., 2012; Williams et al., 2006).”
From Rapid induction of antigen-specific CD4+ T cells is associated with coordinated humoral and cellular immunity to SARS-CoV-2 mRNA vaccination (2021) · cites this paper as Luckheeram et al., 2012

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[71]Lazarevic V Chen X Shim JH T-bet represses TH 17 differentiation by preventing Runx1-mediated activation of the gene encoding RORγt Nature Immunology 2011 12 1 96 104 21151104 PMC3077962
[82]Chen W Jin W Hardegen N Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-β induction of transcription factor Foxp3 Journal of Experimental Medicine 2003 198 12 1875 1886 14676299 PMC2194145
[105]Halonen SK Taylor GA Weiss LM Gamma interferon-induced inhibition of Toxoplasma gondii in astrocytes is mediated by IGTP Infection and Immunity 2001 69 9 5573 5576 11500431 PMC98671
[116]Boehm U Klamp T Groot M Howard JC Cellular responses to interferon-γ Annual Review of Immunology 1997 15 749 795 9143706
[139]Ivanov II McKenzie BS Zhou L The Orphan Nuclear Receptor RORγt Directs the Differentiation Program of Proinflammatory IL-17+ T Helper Cells Cell 2006 126 6 1121 1133 16990136
[142]Korn T Bettelli E Gao W IL-21 initiates an alternative pathway to induce proinflammatory T H17 cells Nature 2007 448 7152 484 487 17581588 PMC3805028
[150]Li MO Wan YY Flavell RA T Cell-Produced Transforming Growth Factor-β1 Controls T Cell Tolerance and Regulates Th1- and Th17-Cell Differentiation Immunity 2007 26 5 579 591 17481928

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Authors: Luckheeram, R. V., Zhou, R., Verma, A. D., & Xia, B.
Affiliations: Wuhan University (CN)
Corresponding author: Xia, Bing
ORCID: Xia, Bing
Venue: Clinical and Developmental Immunology
Publisher: Wiley
Published: 2012
Volume: 2012
Pages: 1-12
ISSN: 1740-2522 (ISSN-L)
1740-2530
DOI: 10.1155/2012/925135
PMC: PMC3312336
OpenAlex: W2074660641
Cited by: 1,381
References: 144
Citations by year: 2026: 79 · 2025: 166 · 2024: 156 · 2023: 178 · 2022: 177 · 2021: 142 · 2020: 116 · 2019: 91 · 2018: 70 · 2017: 65 · 2016: 51 · 2015: 41 · 2014: 27 · 2013: 17 · 2012: 5
FWCI: 2.63
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/3.0/ (unspecified)
Locations: Clinical and Developmental Immunology (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Keywords: CD4+ T cells, T cell differentiation, naive T cells, Th1 cells, Th2 cells, Th17 cells, regulatory T cells, T follicular helper cells, Th9 cells, cytokine signaling, transcription factors, epigenetic modifications, T cell activation
MeSH terms: Animals, Cell Differentiation, Gene Expression Regulation, Humans, Lymphocyte Activation, Transcription Factors, Signal Transduction, Cytokines, Th1 Cells, Th2 Cells, Epigenesis, Genetic, T-Lymphocytes, Regulatory, Mice, Th17 Cells

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CD4 + T Cells: Differentiation and Functions

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