Expanding the effector CD4 T-cell repertoire: the Th17 lineage

Harrington, Laurie E.; Mangan, Paul R.; Weaver, Casey T.

doi:10.1016/j.coi.2006.03.017

Cited by 532 publications

(405 citation statements)

References 53 publications

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“…Although B1 cells have been implicated in the pathophysiology of autoimmune dyscrasias, the mechanisms involved remain incompletely understood. Th17 cells, and Th1 cells, are known to be pathogenic in many autoimmune disease models [10,25]. Thus, it may be speculated that Th17 cell generation constitutes one facet of the autoimmune profile of B1 cells.…”

Section: Discussionmentioning

confidence: 99%

“…Recent evidence has highlighted the role of regulatory T (T reg ) cells in the induction and maintenance of peripheral tolerance and, conversely, the role of T helper (Th)1 and Th17 cells as effectors of inflammatory responses [9,10]. Besides naturally occurring T reg (nT reg ) cells, induced T reg (iT reg ) cells can be converted from naive T cells in the presence of TGF-b [11,12].…”

Section: Introductionmentioning

confidence: 99%

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Reciprocal generation of Th1/Th17 and T_reg cells by B1 and B2 B cells

et al. 2007

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Regulatory T (T reg ) cells are indispensable for maintaining peripheral tolerance, whereas T helper (Th)1 and Th17 cells induce inflammation and tissue destruction. Using Foxp3-GFP knock-in mice, we report a novel regulatory role for B cell subsets in influencing the differentiation of T reg versus Th1/Th17 cells. Peritoneal B1 cells strongly promoted T cell proliferation and cytokine secretion when presenting nominal or allogeneic antigens, as compared to conventional follicular B (B2) cells. However, peritoneal B1 cells largely failed to convert naive Foxp3 -CD4 + T cells into Foxp3 + T reg cells in the presence of TGF-b and IL-2, in marked contrast to conventional B2 cells, which excelled in T reg conversion. Interestingly, under the same T reg conversion conditions, peritoneal B1 cells preferentially promoted Th1 and Th17 cell differentiation. Blockade of CD86 but not CD80 costimulation markedly enhanced T reg cell induction by B1 cells. Thus, B cell antigen presentation function is inversely correlated with de novo T reg cell induction for these B cell subsets. Our findings suggest that B1 and B2 cell subsets play distinct roles in immune regulation by promoting reciprocal differentiation of T cell lineages.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Reciprocal generation of Th1/Th17 and T_reg cells by B1 and B2 B cells

et al. 2007

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“…Surprisingly, we detected an increased production of IL-17, IL-6 and TGF-b cytokines in splenocytes of mice receiving the FC-CD40L vaccine, a pattern consistent with the generation of a Th17-polarized T-cell response. [38][39][40] Several studies have elucidated the role of cytokines involved in the generation of Th17 cells. In mice, IL-6 and TGF-b are critical cytokines involved in Th17 differentiation.…”

Section: Fusion Cell Vaccine With Cd40l Gene Modification E Alvarez Ementioning

confidence: 99%

Dendritic and tumor cell fusions transduced with adenovirus encoding CD40L eradicate B-cell lymphoma and induce a Th17-type response

et al. 2009

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Fusion of dendritic cells and tumor cells (FCs) constitutes a promising tool for generating an antitumor response because of their capacity to present tumor antigens and provide appropriate costimulatory signals. CD40-CD40L interaction has an important role in the maturation and survival of dendritic cells and provides critical help for T-cell priming. In this study, we sought to improve the effectiveness of FC vaccines in a murine model of B-cell lymphoma by engineering FCs to express CD40L by means of an adenovirus encoding CD40L (Adv-CD40L). Before transduction with Adv-CD40L, no CD40L expression was detected in FCs, DCs or tumor cells. The surface expression of CD40L in FC transduced with Adv-CD40L (FC-CD40L) ranged between 50 and 60%. FC-CD40L showed an enhanced expression of CD80, CD86, CD54 and MHC class II molecules and elicited a strong in vitro immune response in a syngeneic mixed lymphocyte reaction. Furthermore, FC-CD40L showed enhanced migration to secondary lymphoid organs. Splenocytes from mice treated with FC-CD40L had a dramatic increase in the production of IL-17, IL-6 and IFN-g, compared with controls. Treatment with the FC-CD40L vaccine induced regression of established tumors and increased survival. Our data demonstrate that FC transduced with Adv-CD40L enhances the antitumor effect of FC vaccines in a murine lymphoma model and this is associated with an increased Th17-type immune response.

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“…While both cytokines can induce IFN-c expression in CD4 + T cells, IL-23, although not involved in Th17 differentiation, plays an important role in maintaining Th17 effector function [3,4]. Th17 cells are responsible for various organ-related autoimmune diseases [5,6], and both IL-23 and the Th17 pathway correlate with disease severity and immunopathology in diverse infections [7][8][9]. These studies suggest that IL-12 and IL-23 have distinct roles in promoting antimicrobial immune responses and diseases in vivo.…”

Section: Introductionmentioning

confidence: 99%

IL‐23 and the Th17 pathway promote inflammation and impair antifungal immune resistance

et al. 2007

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Although inflammation is an essential component of the protective response to fungi, its dysregulation may significantly worsen fungal diseases. We found here that the IL‐23/IL‐17 developmental pathway acted as a negative regulator of the Th1‐mediated immune resistance to fungi and played an inflammatory role previously attributed to uncontrolled Th1 cell responses. Both inflammation and infection were exacerbated by a heightened Th17 response against Candida albicans and Aspergillus fumigatus, two major human fungal pathogens. IL‐23 acted as a molecular connection between uncontrolled fungal growth and inflammation, being produced by dendritic cells in response to a high fungal burden and counter‐regulating IL‐12p70 production. Both IL‐23 and IL‐17 subverted the inflammatory program of neutrophils, which resulted in severe tissue inflammatory pathology associated with infection. Our data are the first demonstrating that the IL‐23/IL‐17 pathway promotes inflammation and susceptibility in an infectious disease model. As IL‐23‐driven inflammation promotes infection and impairs antifungal resistance, modulation of the inflammatory response represents a potential strategy to stimulate protective immune responses to fungi.See accompanying commentary: http://dx.doi.org/10.1002/eji.200737804

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Expanding the effector CD4 T-cell repertoire: the Th17 lineage

Cited by 532 publications

References 53 publications

Reciprocal generation of Th1/Th17 and T_reg cells by B1 and B2 B cells

Reciprocal generation of Th1/Th17 and T_reg cells by B1 and B2 B cells

Dendritic and tumor cell fusions transduced with adenovirus encoding CD40L eradicate B-cell lymphoma and induce a Th17-type response

IL‐23 and the Th17 pathway promote inflammation and impair antifungal immune resistance

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Expanding the effector CD4 T-cell repertoire: the Th17 lineage

Cited by 532 publications

References 53 publications

Reciprocal generation of Th1/Th17 and Treg cells by B1 and B2 B cells

Reciprocal generation of Th1/Th17 and Treg cells by B1 and B2 B cells

Dendritic and tumor cell fusions transduced with adenovirus encoding CD40L eradicate B-cell lymphoma and induce a Th17-type response

IL‐23 and the Th17 pathway promote inflammation and impair antifungal immune resistance

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Reciprocal generation of Th1/Th17 and T_reg cells by B1 and B2 B cells

Reciprocal generation of Th1/Th17 and T_reg cells by B1 and B2 B cells