γδT cells in Juvenile Idiopathic Arthritis: Higher Percentages of Synovial Vδ1+ and Vγ9+ T Cell Subsets Are Associated with Milder Disease

Berkun, Yackov; Bendersky, Anna; Gerstein, Maya; Goldstein, Itamar; Padeh, Shai; Bank, Ilan

doi:10.3899/jrheum.100938

Cited by 23 publications

(22 citation statements)

References 30 publications

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“…Furthermore, SF Vg9 + T cells can induce apoptosis of Sfib that are exposed to a reagent, zoledronate (7). These latter findings suggest an immunological mechanism that may underlie the recently described correlation between recovery from JIA and higher levels of IPP-responsive synovial Vg9 + T cells (13).…”

Section: Discussionsupporting

confidence: 53%

“…Thus, the mean percentage of IFN-gexpressing Vg9 + T cells in PB, but not SF, exceeded that of the CD4 + subset (p = 0.008). In addition, we tested the cytokine production by another gd T cell subset, Vd1, that is equally represented in the synovium of JIA patients (13). High percentages of SF Vd1 + T cells secreted IFN-g and TNF-a (Fig.…”

Section: Cytokine Production By Sf Vg9 + T Cells and Effect Of Ipp Stmentioning

confidence: 99%

“…Although the precise etiology is still unknown, JIA is an autoimmune disease, and T cells are thought to be key players in this process (12). Interestingly, although the Vg9Jg1.2 gene rearrangement is less commonly expressed among synovial fluid (SF) than peripheral blood (PB) gd T cells, IPP was recently found to induce expansion of SF Vg9 + T in virtually all forms of JIA (13,14). However, despite the known proinflammatory potential of Vg9 + T cells in healthy individuals, higher levels of expansion were associated with clinical remission in these patients, suggesting that IPP-induced activation of the cells in some unknown manner contributes to control synovial inflammation (13).…”

mentioning

confidence: 99%

“…Interestingly, although the Vg9Jg1.2 gene rearrangement is less commonly expressed among synovial fluid (SF) than peripheral blood (PB) gd T cells, IPP was recently found to induce expansion of SF Vg9 + T in virtually all forms of JIA (13,14). However, despite the known proinflammatory potential of Vg9 + T cells in healthy individuals, higher levels of expansion were associated with clinical remission in these patients, suggesting that IPP-induced activation of the cells in some unknown manner contributes to control synovial inflammation (13). The experiments described in this paper were undertaken to further delineate functions and cellular interactions of IPP-responsive SF Vg9 + T cells that could be relevant to disease outcomes in these patients.…”

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confidence: 99%

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Cellular Interactions of Synovial Fluid γδ T Cells in Juvenile Idiopathic Arthritis

Bendersky

Marcu-Malina

Berkun

et al. 2012

The Journal of Immunology

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The pathogenesis of juvenile idiopathic arthritis (JIA) is thought to involve multiple components of the cellular immune system, including subsets of γδ T cells. In this study, we conducted experiments to define the functional roles of one of the major synovial fluid (SF) T cell subsets, Vγ9+Vδ2+ (Vγ9+) T cells, in JIA. We found that as opposed to CD4+ T cells, equally high percentages (∼35%) of Vγ9+ T cells in SF and peripheral blood (PB) produced TNF-α and IFN-γ. Furthermore, stimulation with isopentenyl pyrophosphate (IPP), a metabolite in the mevalonate pathway, which is a specific potent Ag for Vγ9Jγ1.2+ T cells, similarly amplified cytokine secretion by SF and PB Vγ9+ T cells. Significantly, the SF subset expressed higher levels of CD69 in situ, suggesting their recent activation. Furthermore, 24-h coculturing with SF-derived fibroblasts enhanced CD69 on the SF > PB Vγ9+ T cells, a phenomenon strongly augmented by zoledronate, a farnesyl pyrophosphate synthase inhibitor that increases endogenous intracellular IPP. Importantly, although Vγ9+ T cell proliferation in response to IPP was significantly lower in SF than PBMC cultures, it could be enhanced by depleting SF CD4+CD25+FOXP3+ cells (regulatory T cells). Furthermore, coculture with the Vγ9+ T cells in medium containing zoledronate or IPP strongly increased SF-derived fibroblasts' apoptosis. The findings that IPP-responsive proinflammatory synovial Vγ9+ T cells for which proliferation is partly controlled by regulatory T cells can recognize and become activated by SF fibroblasts and then induce their apoptosis suggest their crucial role in the pathogenesis and control of synovial inflammation.

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Section: Discussionsupporting

confidence: 53%

Section: Cytokine Production By Sf Vg9 + T Cells and Effect Of Ipp Stmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Cellular Interactions of Synovial Fluid γδ T Cells in Juvenile Idiopathic Arthritis

Bendersky

Marcu-Malina

Berkun

et al. 2012

The Journal of Immunology

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“…120 Moreover, IPPinduced synovial fluid Vc9Vd2 cd-T-cell expansion has been found to ameliorate arthritis. 121 However, the contribution of these regulatory cd-T cells to anti-infection responses is still unclear.…”

Section: Direct Anti-infection Activity Mediated By Cd-t Cells Directmentioning

confidence: 99%

γδ-T cells: an unpolished sword in human anti-infection immunity

et al. 2012

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cd-T cells represent a small population of immune cells, but play an indispensable role in host defenses against exogenous pathogens, immune surveillance of endogenous pathogenesis and even homeostasis of the immune system. Activation and expansion of cd-T cells are generally observed in diverse human infectious diseases and correlate with their progression and prognosis. cd-T cells have both 'innate' and 'adaptive' characteristics in the immune response, and their anti-infection activities are mediated by multiple pathways that are under elaborate regulation by other immune components. In this review, we summarize the current state of the literature and the recent advancements in cd-T cell-mediated immune responses against common human infectious pathogens. Although further investigation is needed to improve our understanding of the characteristics of different cd-T cell subpopulations under specific conditions, cd-T cell-based therapy has great potential for the treatment of infectious diseases.

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Interleukin‐23–Dependent γ/δ T Cells Produce Interleukin‐17 and Accumulate in the Enthesis, Aortic Valve, and Ciliary Body in Mice

Reinhardt

Yevsa

Worbs

et al. 2016

Arthritis & Rheumatology

182

130

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Objective. The spondyloarthritides (SpA) are a group of rheumatic diseases characterized by ossification and inflammation of entheseal tissue, the region where tendon attaches to bone. Interleukin-23 (IL-23) is involved in the pathogenesis of SpA by acting on IL-23 receptor (IL-23R) expressed on enthesis-resident lymphocytes. Upon IL-23 binding, CD31CD42CD82 tissueresident lymphocytes secrete IL-17A and IL-22, leading to inflammation, bone loss, and ossification. Knowledge about enthesis-resident lymphocytes remains fragmentary, and the contribution of entheseal g/d T cells in particular is not clear. This study was undertaken to investigate the presence of g/d T cells in the enthesis.Methods. We used 2-photon microscopy and flow cytometry to analyze entheseal lymphocytes from C57BL/ 6, Tcrd-H2BeGFP, Rorc-GFP, and IL-23R-eGFP mice. To analyze entheseal g/d T cells in IL-232induced inflammation, Tcrd-H2BeGFP mice were crossed with mice of the susceptible B10.RIII background. Hydrodynamic injection of IL-23 minicircle DNA was performed for overexpression of IL-23 and induction of inflammation. Light-sheet fluorescence microscopy was used to visualize arthritic inflammation.

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γδT cells in Juvenile Idiopathic Arthritis: Higher Percentages of Synovial Vδ1+ and Vγ9+ T Cell Subsets Are Associated with Milder Disease

Abstract: The percentage of Vδ1+ and Vγ9+ γδT cells among the SF T cells and their ability to respond to IPP or IL-2 correlated with specific outcomes of JIA, suggesting their role in the immunopathogenesis of this disease.

Cited by 23 publications

References 30 publications

Cellular Interactions of Synovial Fluid γδ T Cells in Juvenile Idiopathic Arthritis

Cellular Interactions of Synovial Fluid γδ T Cells in Juvenile Idiopathic Arthritis

γδ-T cells: an unpolished sword in human anti-infection immunity

Interleukin‐23–Dependent γ/δ T Cells Produce Interleukin‐17 and Accumulate in the Enthesis, Aortic Valve, and Ciliary Body in Mice

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