Generation of follicular helper T cells is mediated by IL-21 but independent of TH1, TH2 or TH17 lineages
By R. Nurieva, Yeonseok Chung, D. Hwang, Xuexian O. Yang, H. Kang, Li Ma, Yi-hong Wang, S. Watowich, A. Jetten, Qiang Tian and 1 more. Immunity, 2008
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After activation, CD4+ helper T (TH) cells differentiate into distinct effector lineages. Although CXCR5+ follicular TH (TFH) cells are important in humoral immunity, their developmental regulation is unclear. Here we show that TFH cells have a distinct gene expression profile from other effector T cells and develop in vivo independent of the TH1 or TH2 lineages. TFH cell generation is regulated by B7h expressed on B cells and, similar to TH17 cell development, is dependent on IL-21, IL-6 and STAT3. However, differentiation of TFH cells, unlike TH17 cells, does not require TGFβ signaling or TH17-specific orphan nuclear receptors RORα and RORγ in vivo. Finally, naïve T cells activated in vitro in the presence of IL-21 but not TGFβ signaling preferentially acquire TFH gene expression and function to promote germinal center reactions in vivo. This study thus demonstrates TFH as a distinct lineage of effector TH differentiation.
Subfields: Immunology
View Paper: https://www.semanticscholar.org/paper/0bbdc75741f68c9bccf0f6b5777b48deb13d5c85
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In Immunology
Citations in the corpus
- CD4+T Cells: Differentiation and Functions (2012, background): “IL6 and IL21 are the main cytokines involved in the differentiation process [103, 104].”
- FOLLICULAR HELPER T CELLS: LINEAGE AND LOCATION (2009, background): “In mouse, gene expression studies of Tfh cells associated with overexpression of ICOS also identified IL-21 and CD200 as preferentially abundant in Tfh cells (Vinuesa et al., 2005a) with Tfh gene expression clustering distinctly when compared to Th1, Th2, and Th17 cells (Nurieva et al., 2008).”
- Human Blood CXCR5+CD4+ T Cells Are Counterparts of T Follicular Cells and Contain Specific Subsets that Differentially Support Antibody Secretion (2011, background): “, 2009), and the interaction with B cells (Nurieva et al., 2008; Zaretsky et al., 2009).”
- Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns (2010, background): “It has recently been shown that a subset of T helper cells known as T follicular helper cells is required for optimal IgG response”
- Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells (2010, methodology): “Th2, Th1, and Th17 cell signatures were generated from published data sets (Nurieva et al., 2008), with 2 as the cut-off for FC over the expression value of two other cell types.”
- Follicular Helper T Cells. (2016, background): “It is upregulated upon CD28 activation (63) and downstream of cytokines activating STAT1 or STAT3, or both.”
- Plasticity of CD4+ T cell lineage differentiation. (2009, background): “Differentiation of these cells requires the cytokine IL-21 (Vogelzang et al., 2008; Nurieva et al., 2008) and may be dependent on the transcription factor Bcl-6 (Fazilleau et al., 2009).”
- Cytokine-secreting follicular T cells shape the antibody repertoire (2009, background): “However, studies suggest that T FH cells do not express these cytokines and thus it remains unknown whether these cytokines act locally or through some bystander mechanism to help B cells in the G”