Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells
By J. O’Shea, W. E. Paul. Science, 2010
1,420 citations recorded by the source corpus.
Critical Mediators Helper T cells are the immune system's ringmasters, having a multiplicity of functions that mediate the body's immune responses to infections. Depending on the type of infection, CD4+ helper T cells respond by secreting specific patterns of cytokines, which provide important cues to other subsets of immune cells. CD4+ T cells with distinct cytokine profiles have been viewed classically as separate lineages; however, there is mounting evidence that these cells may not be terminally differentiated but are in fact quite plastic. O'Shea and Paul (p. 1098) review the current understanding of CD4+ T cell subset differentiation and the underlying mechanisms that drive cell-lineage commitment. CD4+ T cells are critical for host defense but are also major drivers of immune-mediated disease. These T cells specialize to become distinct subsets and produce restricted patterns of cytokines, which are tailored to combat various microbial pathogens. Although classically viewed as distinct lineages, recent work calls into question whether helper CD4+ T cell subsets are more appropriately viewed as terminally differentiated cells or works in progress. Herein, we review recent advances that pertain to this topic and the mechanisms that contribute to helper CD4+ T cell commitment and plasticity. The therapeutic implications of these new findings are also considered.
Subfields: Immunology
View Paper: https://www.semanticscholar.org/paper/780e5a63abd8bfe9df06938885cdf5c7074199a7
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Citations in the corpus
- Macrophage Polarization in Physiological and Pathological Pregnancy (2019, background): “Notably, only IL-4 and IL-13 directly induce M2 macrophage activation, whereas other cytokines (such as IL-33 and IL-25) amplify M2 macrophage activation by producing Th2 cytokines (17).”
- NF-κB signaling in inflammation (2017, positive): “29,30 M1 macrophages are characterized by the production of pro-inflammatory cytokines, such as IL-1, IL-6, IL-12, TNF-α and chemokines, involved in various inflammatory processes.”
- The expanding family of innate lymphoid cells: regulators and effectors of immunity and tissue remodeling (2011, background): “However, just as there is a growing realization that CD4 + helper T cells are more 'plastic' in their cytokine production than previously though”
- T follicular helper cell differentiation, function, and roles in disease (2014, background): “Even this nomenclature is imperfect, given the evidence of reversible plasticity by most CD4+ T cell types (O’Shea and Paul, 2010).”
- Engineering T cells with Customized Therapeutic Response Programs Using Synthetic Notch Receptors (2016, neutral): “T helper cell 1 (Th1) or T helper cell 2 (Th2) T cells are two canonical CD4 T cell fate choices that are controlled by the master regulator transcription factors, Tbet and GATA3, respectively (Figure 3A) (O’Shea and Paul, 2010).”
- Interleukin-2 at the Crossroads of Effector Responses, Tolerance, and Immunotherapy (2013, positive): “These differentiation pathways are not necessarily terminal, however, and subsets of Th cells can acquire the ability to produce other Th cell-specific cytokine(s) (O’Shea and Paul, 2010).”
- AN INTERACTION BETWEEN KYNURENINE AND THE ARYL HYDROCARBON RECEPTOR CAN GENERATE REGULATORY T CELLS, (2010, background): “Interestingly, these new data have led investigators to question previously held beliefs about terminal cell differentiation and stability of Tregs, as the ability of Tregs to redifferentiate into Th17 cells in the appropriate inflammatory milieu has now been described (8, 9).”
- CD4⁺ follicular helper T cell infiltration predicts breast cancer survival. (2013, neutral): “This view is complicated by the plasticity of Th differentiation (56), which involves shared surface receptors and cytokines that are often rapidly modulated in time and place, making it frequently difficult to clearly discriminate the type of response(s).”
- Fate mapping of interleukin 17-producing T cells in inflammatory responses (2011, background): “To some extent the unusual biology of the T H 17 subset has triggered these questions, although they are by no means restricted to T H 17 cell biology and indeed are now being explored in other effector T cell subsets as wel”
- The light and dark sides of intestinal intraepithelial lymphocytes (2011, neutral): “Finally, recent data have highlighted the intriguing phenomena of plasticity of CD4 + effector and regulatory T cell”
- OMIP‐018: Chemokine receptor expression on human T helper cells (2013, background): “T cell polarization is regulated by lineage-specifying transcription factors and leads to the up-regulation of a plethora of cytokines which characterize different types of effector T cells (2).”
- NK cell development, homeostasis and function: parallels with CD8+ T cells (2011, background): “In addition, transcription factors that dictate the differentiation of mature naive T cells into effector cells have also been characterized, including T-bet for T helper 1 (T H 1) cells, GATA3 for T H 2 cells, B cell lymphoma 6 (BCL-6) for T follicular helper cells, forkhead box P3 (FOXP3) for regu”
- Macrophage plasticity and polarization: in vivo veritas. (2012, neutral): “org Volume 122 Number 3 March 2012 174(10):6095–6104.”
- Alternative activation of macrophages: mechanism and functions. (2010, background): “Cytokines in AAM Induction IL-4 and IL-13 are the prototypical direct inducers of AAMs, but other cytokines such as IL-33 and IL-25 amplify AAM induction indirectly, through Th2 cells (for review on CD4+ T cell heterogeneity, see O’Shea and Paul, 2010).”