Interleukin 7 Is a Potent Co-Stimulator of Myelin Specific T Cells That Enhances the Adoptive Transfer of Experimental Autoimmune Encephalomyelitis

Bebo, Bruce F.; Schuster, Jeanette C.; Adlard, Kirsten; Vandenbark, Arthur A.; Offner, Halina

doi:10.1006/cyto.1999.0564

Cited by 17 publications

(13 citation statements)

References 42 publications

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“…7), suggesting that deficient Th1 differentiation may also contribute to the decreased clinical and pathological signs of EAE in IL-7Rα −/− mice. Earlier studies have shown that adoptive transfer of encephalitogenic T cells cultured in the presence of rIL-7 resulted in severe and prolonged EAE compared to the control and in vitro treatment with IL-7 resulted in increased IFNγ secretion and Ag-specific T cell proliferation 31. Our findings are consistent with earlier reports showing upregulation of IFNγ and IL-17 production by IL-7 in a model of rheumatoid arthritis 32,33.…”

Section: Discussionsupporting

confidence: 93%

IL-7Rα confers susceptibility to experimental autoimmune encephalomyelitis

2010

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Multiple sclerosis (MS) is a neurological disorder that causes paralysis in young adults and affects women more frequently than men. The etiology of MS is not known, but it is generally viewed as an autoimmune disease of the central nervous system (CNS), influenced by genetic and environmental factors. Recent studies have identified interleukin 7 receptor alpha (IL-7Rα) as a risk factor for multiple sclerosis. But the role of IL-7Rα in experimental autoimmune encephalomyelitis (EAE) model of MS is not known. In this study we demonstrate that IL-7Rα deficient (IL-7Rα−/−) mice remain resistant to MOGp35-55-induced EAE. When compared to C57BL/6 wild type mice, IL-7Rα−/− mice showed less severe inflammation and demyelination in the CNS. The attenuation of EAE in IL-7Rα−/− mice was associated with a decrease in T helper (Th) 1 and Th17 responses in the CNS and lymphoid organs. IL-7Rα−/− mice also showed an increase in Th2 response and CD4+Foxp3+ regulatory T cells. These findings highlight that IL-7Rα confers susceptibility by influencing autoimmune Th1/Th17 responses in EAE model of MS.

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Section: Discussionsupporting

confidence: 93%

IL-7Rα confers susceptibility to experimental autoimmune encephalomyelitis

2010

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“…IL-7 has been shown to increase T-cell proliferation 16 and reactivity 17 to myelin antigens in MS and in EAE. 18 In the latter study, IL-7 expanded T cells were also found to cause more severe EAE when adoptively transferred to naïve recipient mice. More recently, a microarray study showed IL-7R cDNA expression to be significantly increased in PBMCs from MS patients with relapsing -remitting disease, compared with normal controls.…”

mentioning

confidence: 84%

Identification of 11 novel and common single nucleotide polymorphisms in the interleukin-7 receptor-α gene and their associations with multiple sclerosis

et al. 2003

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We have investigated the interleukin-7 receptor (IL-7R) a-chain gene as a positional and functional candidate gene for susceptibility to multiple sclerosis (MS), in view of its chromosomal location on 5p14-p12, a region that has shown suggestive linkage in MS genome screens, and its role in T-and B-cell proliferation and reactivity. Amplification and DNA sequencing of the IL-7Ra gene in pooled and individual samples identified 13 single nucleotide polymorphisms (SNPs), 11 of which are novel, including three in the promoter region, three in exons encoding amino-acid changes (ACC(Thr)66ATC(Ile), ATC(Ile)244ACC(Thr), ATC(Ile)336GTC(Val)), four in introns and one in the 3 0 untranslated region. Four IL-7R haplotypes were identified for nine SNPs, showing linkage disequilibrium across the gene, and allowing haplotype frequency determination from just three of the nine SNPs. Genotyping of the À504 polymorphism in 101 MS and 90 controls showed a suggestive (P ¼ 0.1) association of the T allele with MS; however, this was not supported by transmission disequilibrium testing in 186 MS trio families (P ¼ 0.8). There were trends towards an increase of the GTG+ haplotype (odds ratio ¼ 1.45), and underrepresentation of the TTA+ haplotype (OR ¼ 0.65) in DRB1*1501-positive MS cases, suggesting that larger sample sizes and comparison in more defined MS patient groups may support an association with the IL-7R gene. These polymorphisms would also be useful for studying genetic associations with other immunologic diseases.

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“…18 Increased IL-7 (not TNFa 34 57 ) induces cell contact dependent, 34 61 cytokine activated T cells (3) causing a spreading of T cell activation associated with autoantigenic recognition (possibly intermediate affinity self-antigens). 62 This can operate independent of TNFa (4). Such cytokine activated, bystander T cells in turn stimulate monocytic cells and possibly B cells (5).…”

Section: Il-7 In Other Chronic Inflammatory (Autoimmune) Diseasesmentioning

confidence: 99%