Regulation of Experimental Autoimmune Encephalomyelitis by Interleukin‐12

Leonard, John P.; Waldburger, Kristine E.; Goldman, Samuel J.

doi:10.1111/j.1749-6632.1996.tb52671.x

Cited by 36 publications

(11 citation statements)

References 23 publications

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“…We confirmed these results using anti-IL-12/IL-23 blocking Abs (34) in WT recipient mice (Fig. 6F), excluding the possibility that the disease development in genetically modified animals was due to developmental changes of their immune system.…”

Section: Absence or Neutralization Of Both Il-12 And Il-23 During Thesupporting

confidence: 74%

IL-23 Is Critical in the Induction but Not in the Effector Phase of Experimental Autoimmune Encephalomyelitis

Thakker

Leach²,

Kuang³

et al. 2007

The Journal of Immunology

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153

118

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Experimental autoimmune encephalomyelitis (EAE), a T cell-mediated inflammatory disease of the CNS, is a rodent model of human multiple sclerosis. IL-23 is one of the critical cytokines in EAE development and is currently believed to be involved in the maintenance of encephalitogenic responses during the tissue damage effector phase of the disease. In this study, we show that encephalitogenic T cells from myelin oligodendrocyte glycopeptide (MOG)-immunized wild-type (WT) mice caused indistinguishable disease when adoptively transferred to WT or IL-23-deficient (p19 knockout (KO)) recipient mice, demonstrating that once encephalitogenic cells have been generated, EAE can develop in the complete absence of IL-23. Furthermore, IL-12/23 double-deficient (p35/p19 double KO) recipient mice developed EAE that was indistinguishable from WT recipients, indicating that IL-12 did not compensate for IL-23 deficiency during the effector phase of EAE. In contrast, MOG-specific T cells from p19KO mice induced EAE with delayed onset and much lower severity when transferred to WT recipient mice as compared with the EAE that was induced by cells from WT controls. MOG-specific T cells from p19KO mice were highly deficient in the production of IFN-γ, IL-17A, and TNF, indicating that IL-23 plays a critical role in development of encephalitogenic T cells and facilitates the development of T cells toward both Th1 and Th17 pathways.

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Section: Absence or Neutralization Of Both Il-12 And Il-23 During Thesupporting

confidence: 74%

IL-23 Is Critical in the Induction but Not in the Effector Phase of Experimental Autoimmune Encephalomyelitis

Thakker

Leach²,

Kuang³

et al. 2007

The Journal of Immunology

Self Cite

153

118

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“…Many data on a major role for IL-12 in multiple sclerosis have been obtained from rodent studies of the experimental autoimmune encephalomyelitis. However, most of the experiments were performed primarily through the use of neutralizing antibodies against p40 that affect both IL-12 and IL-23 (10,29,30). Recently, Cua et al (13) compared the susceptibility of mice FIG.…”

Section: Fig 5 Intracellular Ifn-␥ Staining Of Hcv-specific Cd8mentioning

confidence: 99%

Adjuvant Activities of Novel Cytokines, Interleukin-23 (IL-23) and IL-27, for Induction of Hepatitis C Virus-Specific Cytotoxic T Lymphocytes in HLA-A*0201 Transgenic Mice

Matsui

Moriya

Belladonna

et al. 2004

J Virol

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CD8ϩ cytotoxic T lymphocytes (CTLs) recognize virus-derived peptides in association with major histocompatibility complex class I molecules on the surface of antigen-presenting cells and kill the virus-infected target cells. There are a number of evidences showing that CTLs play a central role in the clearance of pathogenic viruses (67). In case of hepatitis C virus (HCV) infection, vigorous HCV-specific CTL responses existed in the persons resolving acute HCV infection (27). In the experimental model, chimpanzees who cleared HCV generated strong CTL but poor antibody responses, whereas other chimpanzees developing chronic hepatitis generated much weaker CTL response (12). Thus, spontaneous resolution of HCV is likely to be associated with HCV-specific CTLs rather than neutralizing antibodies (12,18,27,58). However, Ͼ60% of HCV-infected individuals turn out to have chronic hepatitis (1). Chronic HCV hepatitis eventually progresses to cirrhosis and hepatocellular carcinoma (53). In the chronic stage, HCVspecific CTLs are detectable in both peripheral blood and liver, but the precursor frequency of HCV-specific CTLs is extremely low (27,50,51). Therefore, enhancement of HCVspecific CTL induction in HCV-infected individuals should be considered to be a strategy to clear the virus. DNA vaccination has been proven to be a useful strategy for inducing both humoral and cellular immune responses (19). DNA vaccine safely mimics the effect of live, attenuated virusbased vaccine to generate a long-lasting CTL response. However, the efficiency of DNA vaccine is sometimes quite low and, therefore, several modifications have been attempted in recent years (19). Thus far, the most successful protocol of DNA immunization for CTL induction is likely to be a consecutive immunization involving priming with plasmid DNA and boosting with recombinant virus (2,24,35,43,54). The rationale behind this strategy is that DNA priming elicits low-level but persistent immunity, followed by strong boosting with virus encoding the same recombinant antigen as the DNA encodes. This regimen of the consecutive immunization has been proven to be efficient for CTL induction by many groups (2,24,35,37,43,54). Recently, McConkey et al. (37) have shown that the prime-boost immunization induced high frequencies of antigen-specific T-cell responses to malaria antigen and displayed partial protection in humans.Interleukin-12 (IL-12) is a heterodimeric proinflammatory cytokine formed by a 35-kDa light chain (p35) and a 40-kDa heavy chain (p40) (57). This cytokine is a dominant factor in the differentiation of T helper type 1 (Th1) cells and plays an essential role in a link between innate and adaptive immunities (60). Recently, two novel polypeptides, p19 (42) and p28 (48), have been identified by searching the databases with a computationally derived profile of IL-6. These factors do not show

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“…Numerous studies have established IL-12 as an important factor for the differentiation of naive T cells into IFN-g-producing Th1 cells, which are essential for cell-mediated immunity, including antimicrobial responses and tumor suppression (3)(4)(5). Over the past decade, IL-12-driven Th1 cells were also shown to be essential for the induction of autoimmune diseases, primarily through investigations using IL-12p40 -/-mice and IL-12p40-neutralizing antibodies (6)(7)(8)(9)(10)(11)(12)(13). However, mice lacking certain components of the Th1/IFN-g pathway (IL-12p35 -/-, IL-12b1 -/-, IFN-g -/-, IFN-gR -/-, and STAT1; R, receptor) are highly susceptible to inflammatory autoimmune diseases, indicating that these regulatory factors are not always required for disease induction (14)(15)(16)(17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

Anti-IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis

Chen¹,

Langrish²,

McKenzie³

et al. 2006

Journal of Clinical Investigation

519

394

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Regulation of Experimental Autoimmune Encephalomyelitis by Interleukin‐12

Cited by 36 publications

References 23 publications

IL-23 Is Critical in the Induction but Not in the Effector Phase of Experimental Autoimmune Encephalomyelitis

IL-23 Is Critical in the Induction but Not in the Effector Phase of Experimental Autoimmune Encephalomyelitis

Adjuvant Activities of Novel Cytokines, Interleukin-23 (IL-23) and IL-27, for Induction of Hepatitis C Virus-Specific Cytotoxic T Lymphocytes in HLA-A*0201 Transgenic Mice

Anti-IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis

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