Depletion of γ/δ T cells does not prevent or ameliorate, but rather aggravates, rat adjuvant arthritis

Pelegrí, Carme; Kühnlein, P.; Buchner, Eberhard; Schmidt, C.; Franch, Àngels; Castell, Margarida; Hünig, Thomas; Emmrich, Frank; Kinne, Raimund W.

doi:10.1002/art.1780390206

Cited by 47 publications

(35 citation statements)

References 35 publications

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“…Some evidence suggests that ␥␦ T cells may be beneficial in certain autoimmune models. Both collagen-induced arthritis in mice (45) and adjuvant arthritis in rats (46) are made worse by depletion of ␥␦ T cells, as is the lupus-like disease in MRL-lpr mice lacking ␥␦ T cells (47). Similar results have been observed in a model of orchitis in which ␥␦ depletion accelerated the inflammatory response (48).…”

Section: Discussionmentioning

confidence: 99%

High Expression of Fas Ligand by Synovial Fluid-Derived γδ T Cells in Lyme Arthritis

Roessner¹,

Wolfe²,

Shi³

et al. 2003

The Journal of Immunology

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γδ T cells accumulate at epithelial barriers and at sites of inflammation in various infectious and autoimmune diseases, yet little is understood about the function of tissue-infiltrating γδ T cells. We observe that γδ T cells of the Vδ1 subset accumulate in synovial fluid of human Lyme arthritis and are intensely cytolytic toward a wide array of target cells. Particularly striking is that the cytolytic activity is highly prolonged, lasting for at least 3 wk after stimulation of the γδ T cells with Borrelia burgdorferi. Cytolysis is largely Fas dependent and results from very high and prolonged expression of surface Fas ligand, which is transcriptionally regulated. This also manifests in a substantial level of self-induced apoptosis of the γδ T cells. In this capacity, certain γδ T cell subsets may serve as cytolytic sentinels at sites of inflammation, and perhaps at epithelial barriers.

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Section: Discussionmentioning

confidence: 99%

High Expression of Fas Ligand by Synovial Fluid-Derived γδ T Cells in Lyme Arthritis

Roessner¹,

Wolfe²,

Shi³

et al. 2003

The Journal of Immunology

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“…Some models of autoimmunity have reported improvement with depletion of ␥␦ T cells, whereas others were provoked (37,39,40). This may reflect in part how each particular autoimmune syndrome is affected by biases toward Th1 versus Th2 cytokine environments.…”

Section: Fig 2 Mice Bearing Mutations In Fas Ormentioning

confidence: 99%

“…Thus, both collagen-induced arthritis in mice (41) and adjuvant arthritis in rats (39) were made worse after the administration of anti-␥␦ antibody. The Th1 cytokine environment observed in inflamed joint fluid in Lyme arthritis and rheumatoid arthritis (48,60) might reflect the influence of synovial ␥␦ T cells, which accumulate to significant levels in the synovium in both of these diseases (2,58).…”

Section: Vol 76 2002mentioning

confidence: 99%

γδ T Cells Promote a Th1 Response during Coxsackievirus B3 Infection In Vivo: Role of Fas and Fas Ligand

Huber¹,

Shi

Budd

2002

J Virol

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Coxsackieviruses are closely associated with myocarditis and dilated cardiomyopathy in humans. Serum levels of soluble Fas (CD95) and Fas ligand (FasL) predict disease course in patients with acute myocarditis, with the highest levels of these factors occurring in patients with a fatal outcome (11). Fasdependent apoptosis of cardiac myocytes is observed in some cases of clinical and experimental myocarditis (10,18,54). In other instances, apoptosis may be restricted to the myocardial inflammatory cell infiltrate and occurs primarily in CD4 ϩ T cells (7,18,27,59). In the case of direct Fas-dependent apoptosis of cardiac myocytes, the mechanism by which Fas contributes to pathogenesis in myocarditis is self-evident. It is less clear whether Fas-dependent apoptosis affects pathogenicity when only the infiltrating inflammatory cells die.We have previously reported that coxsackievirus B3 (CVB3)-induced myocarditis in BALB/c mice depends upon generation of CD4 ϩ Th1 (gamma interferon [IFN-␥ ϩ ]) cell responses and that CD4 ϩ Th2 cell responses protect against CVB3-induced disease (24). T cells expressing the ␥␦ T-cell receptor (TCR) regulate the CD4 ϩ Th phenotype in vivo. Although cytokines produced by ␥␦ T cells may partially contribute to their modulation of the CD4 ϩ cell response (20), direct cell-cell contact between the ␥␦ ϩ and CD4 ϩ cells is additionally important in vitro (19). In this study, we provide evidence in vivo that ␥␦ T-cell modulation of the CD4 ϩ cytokine phenotype requires Fas-FasL interaction to promote a pathogenic Th1 response. MATERIALS AND METHODS Mice. BALB/c, MRLϩ/ϩ , MRL lpr/lpr (lpr), and MRL gld/gld (gld) mice were originally purchased from Jackson Laboratories (Bar Harbor, Maine). Breeding colonies were maintained at the University of Vermont. Male mice 5 to 8 weeks of age were used in all experiments.Infection. Animals received injections of 10 5 PFU of CVB3 (variant H3-49) intraperitoneally in 0.5 ml of phosphate-buffered saline (PBS) (24). Animals were euthanatized 7 days after infection by intraperitoneal injection of 120 mg of sodium pentobarbital/kg of body weight in 0.5 ml of PBS.Histology. Hearts were removed and divided in half, and the apex portion of the heart was fixed in 10% buffered formalin. Tissue was paraffin embedded, sectioned, stained with hematoxylin and eosin, and evaluated for inflammation by image analysis using the procedure reported by Knowlton et al. (29). Briefly, heart sections were viewed in transmitted light mode with an Olympus BX50 compound light microscope, and true-color digital images were captured with a Sony DXC-960MD/LLP video camera connected to a video frame grabber on a SUN SPARCstation5. Image processing and analysis were done using IMIX software (Princeton Gamma Tech Inc., Princeton, N.J.).Virus titer. The remaining cardiac tissue not used for histology was homogenized in RPMI 1640 medium containing 5% fetal bovine serum (FBS), centrifuged at 300 ϫ g to remove cellular debris, serially titrated using 10-fold dilutions, and added to HeLa cell...

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“…T cells expressing the ␥␦ T-cell receptor (TcR) accumulate at inflammatory sites and can modulate disease susceptibility by either promoting or suppressing inflammation (4,6,9,13,17,20,27,28,35,36,38,41,44). In some models, ␥␦ ϩ T cells have both pro-and anti-inflammatory effects at different times in the disease process.…”

Section: Two Coxsackievirus B3 (Cvb3) Variants (H3 Andmentioning

confidence: 99%

Cytokine Production by Vγ⁺-T-Cell Subsets Is an Important Factor Determining CD4⁺-Th-Cell Phenotype and Susceptibility of BALB/c Mice to Coxsackievirus B3-Induced Myocarditis

Huber

Graveline

Born

et al. 2001

J Virol

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Depletion of γ/δ T cells does not prevent or ameliorate, but rather aggravates, rat adjuvant arthritis

Cited by 47 publications

References 35 publications

High Expression of Fas Ligand by Synovial Fluid-Derived γδ T Cells in Lyme Arthritis

High Expression of Fas Ligand by Synovial Fluid-Derived γδ T Cells in Lyme Arthritis

γδ T Cells Promote a Th1 Response during Coxsackievirus B3 Infection In Vivo: Role of Fas and Fas Ligand

Cytokine Production by Vγ⁺-T-Cell Subsets Is an Important Factor Determining CD4⁺-Th-Cell Phenotype and Susceptibility of BALB/c Mice to Coxsackievirus B3-Induced Myocarditis

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Depletion of γ/δ T cells does not prevent or ameliorate, but rather aggravates, rat adjuvant arthritis

Cited by 47 publications

References 35 publications

High Expression of Fas Ligand by Synovial Fluid-Derived γδ T Cells in Lyme Arthritis

High Expression of Fas Ligand by Synovial Fluid-Derived γδ T Cells in Lyme Arthritis

γδ T Cells Promote a Th1 Response during Coxsackievirus B3 Infection In Vivo: Role of Fas and Fas Ligand

Cytokine Production by Vγ+-T-Cell Subsets Is an Important Factor Determining CD4+-Th-Cell Phenotype and Susceptibility of BALB/c Mice to Coxsackievirus B3-Induced Myocarditis

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Cytokine Production by Vγ⁺-T-Cell Subsets Is an Important Factor Determining CD4⁺-Th-Cell Phenotype and Susceptibility of BALB/c Mice to Coxsackievirus B3-Induced Myocarditis