Generation of T Follicular Helper Cells Is Mediated by Interleukin-21 but Independent of T Helper 1, 2, or 17 Cell Lineages

Nurieva, Roza; Chung, Yeonseok; Hwang, Daehee; Yang, Xuexian O.; Kang, Hong Soon; Ma, Li; Wang, Yi Hong; Watowich, Stephanie S.; Jetten, Anton M.; Tian, Qiang; Chen, Dong

doi:10.1016/j.immuni.2008.07.010

Cited by 273 publications

(453 citation statements)

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“…The data showed that anti-V ASCs induced by targeting CD8a À DCs were dramatically decreased in CXCR5-KO (Breitfeld et al, 2000), SAP-KO (Qi et al, 2008), and IL-21 receptor (R)-KO (Nurieva et al, 2008) mice ( Figure 1C), but this decrease was not observed in IL12p40-KO (Ma et al, 2009;Mosmann and Coffman, 1989) or IL-4R-KO (Kaplan et al, 1996) mice ( Figure 1D). Taken together, these data indicated that CD8a À DCs enhance antigen-specific ASCs in a Tfh cell-dependent manner rather than a Th1 cell-or Th2 cell-dependent manner.…”

Section: Resultsmentioning

confidence: 97%

CD8α− Dendritic Cells Induce Antigen-Specific T Follicular Helper Cells Generating Efficient Humoral Immune Responses

et al. 2015

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Recent studies on T follicular helper (Tfh) cells have significantly advanced our understanding of T cell-dependent B cell responses. However, little is known about the early stage of Tfh cell commitment by dendritic cells (DCs), particularly by the conventional CD8α(+) and CD8α(-) DC subsets. We show that CD8α(-) DCs localized at the interfollicular zone play a pivotal role in the induction of antigen-specific Tfh cells by upregulating the expression of Icosl and Ox40l through the non-canonical NF-κB signaling pathway. Tfh cells induced by CD8α(-) DCs function as true B cell helpers, resulting in significantly increased humoral immune responses against various human pathogenic antigens, including Yersinia pestis LcrV, HIV Gag, and hepatitis B surface antigen. Our findings uncover a mechanistic role of CD8α(-) DCs in the initiation of Tfh cell differentiation and thereby provide a rationale for investigating CD8α(-) DCs in enhancing antigen-specific humoral immune responses for improving vaccines and therapeutics.

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Section: Resultsmentioning

confidence: 97%

CD8α− Dendritic Cells Induce Antigen-Specific T Follicular Helper Cells Generating Efficient Humoral Immune Responses

et al. 2015

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“…Additional signals from the microenvironment such as the cytokines IL-6 and IL-21 and the subsequent activation of STAT3 appear to reinforce the generation of B helper capacity [26,27] that, at this early stage, remains compatible with multiple differentiation programs [28]. Several studies using mice in which IL-21-IL-21R interactions have been disrupted have demonstrated an important role for IL-21 in differentiation of multiple T helper subsets [26,[29][30][31].…”

Section: Differentiation Of Tfh Cellsmentioning

confidence: 99%

“…Several studies using mice in which IL-21-IL-21R interactions have been disrupted have demonstrated an important role for IL-21 in differentiation of multiple T helper subsets [26,[29][30][31]. For Tfh cells, IL-21 exhibits an autocrine role in Tfh cell differentiation [26,30] that precedes the acquisition of B cell follicle homing capacity [30]. Elevated expression of IL-21 is a characteristic feature of Tfh cells and recent studies have demonstrated greater levels of IL-21 in GC Tfh cells than in Th2 cells located in the lungs [13,17,18 ,32 ].…”

Section: Differentiation Of Tfh Cellsmentioning

confidence: 99%

Lineage specification and heterogeneity of T follicular helper cells

Yu¹,

Batten²,

Mackay³

et al. 2009

Current Opinion in Immunology

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“…Multiple studies revealed the important role of IL-21 in the GC formation, antibody isotype switching, and generation of GC T cells (Linterman et al, 2010;Nurieva et al, 2008;Vogelzang et al, 2008;Zotos et al, 2010). Indeed, not only B cells but also some activated CD4 þ T cells move from the outer follicular zone into the GCs and become T FH cells.…”

Section: Germinal Centersmentioning

confidence: 99%