Su.122. Cd8+ Il-17 Producing T-Cells Are Important in Effector Functions for the Elicitation of Contact Hypersensitivity

He, Dao-Yao; Wu, Lizhi; Kim, Hee Kyung; Li, Hui; Elmets, Craig A.; Xu, Hui

doi:10.1016/j.clim.2006.04.549

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“…However, we cannot exclude that other cell types than CD4 1 T cells contribute to pathogenic IL-17 production. CD8 1 T cells, macrophages and neutrophils are reported to be able to express IL-17 [34][35][36]. However, CD8 1 T cells are of minor importance in AIA but macrophages and neutrophils are involved in AIA development [37,38].…”

Section: Discussionmentioning

confidence: 99%

In vitro‐induced Th17 cells fail to induce inflammation in vivo and show an impaired migration into inflamed sites

et al. 2010

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Recently, IL-17 produced by Th17 cells was described as pro-inflammatory cytokine with an eminent role in autoimmune diseases, e.g. rheumatoid arthritis. A lack of IL-17 leads to amelioration of collagen-induced arthritis. IL-17 induction in naïve CD41 T cells depends on IL-6 and TGF-b and is enhanced by IL-23. The in vivo inflammatory potential of in vitroprimed Th17 cells however, remains unclear. Here, we show that, although IL-17 neutralisation results in amelioration of murine OVA-induced arthritis, in vitro-primed Th17 cells cannot exacerbate arthritic symptoms after adoptive transfer. Furthermore, Th17 cells cannot induce an inflammatory delayed type hypersensitivity reaction because they fail to migrate into inflamed sites, possibly due to the lack of CXCR3 expression. Also, re-isolated Th17 cells acquired IFN-c expression, indicating instability of the Th17 phenotype. Taken together, the data show that IL-6, TGF-b and IL-23 might not provide sufficient signals to induce ''fully qualified'' Th17 cells.Key words: Cell migration . Inflammation . Th17 cells IntroductionIn the last years, the pro-inflammatory cytokines IL-23 and IL-17 came into focus to play a major role in inflammatory autoimmune diseases. IL-23, a heterodimeric protein consisting of p40 (shared subunit with IL-12) and p19, was identified as an important factor to induce or maintain inflammatory diseases, for p19-deficient mice are resistant to EAE and colitis [1,2]. IL-17 acts on multiple cell types to evoke the release of other pro-inflammatory cytokines like TNF-a, IL-1b or IL-6 as well as chemokines like IL-8 to attract neutrophils or macrophages to the inflamed site [3,4]. This may lead to a rising inflammatory response. In addition, IL-17 directly causes bone and cartilage destruction via upregulation of RANK-L and therefore, an eminent role of IL-17 in autoimmune diseases, like rheumatoid arthritis, was reported [5,6]. In 2006 Veldhoen et al. and others showed that the combination of IL-6 and TGF-b is sufficient to induce IL-17 expression by CD4 T cells in vitro [7]. Furthermore, by blocking Th1 and Th2 differentiation pathways, the efficiency of Th17 differentiation can be enhanced. Therefore, IL-17-producing Th cells were claimed to represent a distinct Th-cell lineage, termed Th17 cells [7][8][9]. However, IL-1b was reported to be necessary for Th17 induction in vivo and IL-6-independent pathways for IL-17 induction may exist, for IL-6-deficient mice show diminished but detectable levels of Th17 cells [10,11]. RORgT was claimed to be the Th17 lineage-specific transcription factor and sufficient to Ã These authors contributed equally to this work. To directly address the question on the role of joint-specific Th17 cells for arthritis pathogenesis we employed the OVAinduced arthritis (OIA) model. This arthritis model allows the direct analysis of OVA-specific T cells upon adoptive transfer in vivo. Using OIA and delayed type hypersensitivity (DTH) reaction, we show that in vitro-primed Th17 cells lack proinflammatory potential in vi...

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