Abstracts (complete list) - Wissenschaft Online

Marko Janke, Michael Peine, Thordis Hohnstein, Lars Morawietz, Alexander Scheffold
THE ROLE OF TH1 AND TH17 T CELLS IN INFLAMMATORY
REACTIONS IN VIVO
Introduction:
The role of Interferon-γ (IFN-γ) produced by Th1 cells in vivo is controversially
discussed. While Th1 cells can induce inflammatory reactions, like delayed type
hypersensitivity (DTH), neutralisation of the prototypic Th1 cytokine IFN-γ leads to an
even more pronounced DTH or a more severe inflammatory arthritis. Recently, IL-17
produced by Th17 cells was shown to act highly pro-inflammatory in inflammatory
autoimmune diseases, like collagen-induced arthritis. Therefore, our aim was to analyse
the role of Th1 vs Th17 cells in inflammatory reactions using DTH or the ovalbumininduced
arthritis model (OIA). In this model, arthritis is induced by intra-articular (i.a.)
injection of ovalbumin into Ova-immunised mice.
Results:
We show that IFN-γ as well as IL-17 is produced to equal amounts by ex vivo isolated
antigen-specific CD4+ T cells taken from arthritic mice. Interestingly, in anti-IL-17
treated mice arthritis was significantly ameliorated. In contrast, the transfer of in vitro
generated Th17 cells did not enhance arthritis symptoms, while Th1 cells did enhance
arthritis. Similarly, Th17 cells only evoked a mild DTH reaction in sharp contrast to Th1
cells, which induced strong and long-lasting DTH. This difference was probably caused
by different migratory capacity into inflammatory sites, since Th1 but not Th17 cells
migrated into the inflammatory foot and the draining lymph node.
Conclusion:
In vitro generated Th1 cells exert the expected pro-inflammatory function in vivo. In
contrast, while IL-17 seems to increase OIA severity, in vitro generated Th17 cells failed
to enhance or evoke inflammatory reactions, like arthritis or DTH. Thus, IL-17
producing cells generated by currently described in vitro protocols do not possess the
full functional potential of there in vivo counterparts. It will be important to determine
the missing parameters required for full Th17 functional activity, in addition to secretion
of IL-17.