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IL-17-producing thymocytes have been recently described and are believed to play a role as an immune cell population which is able to react against microbial components rapidly. For this reason, we here investigated the ability of two microbial stimulants, bacterial flagellin (a ligand for TLR5) and diphtheria toxin from Corynebacterium diphtheriae, to activate or co-activate (together with α-CD3 stimulation) thymocyte cytokine production. We find that both bacterial molecules do not induce cytokine-production by themselves, but co-activate IL-17-producing thymocytes together with α-CD3. Since diphtheria toxin is unlikely to affect mouse cells through the same mechanism as the lethal effect on human cells, our results point to an additional mechanism of diphtheria toxin to act on immune cells. However, there is no additive or super-additive effect after stimulation with diphtheria toxin combined with flagellin and α-CD3 co-activation, which suggests that microbial stimuli used in this study can only activate a limited number of IL-17 producing thymocytes., (Copyright © 2013. Published by Elsevier Ltd.)

Interleukin (IL-)17 is a potent proinflammatory cytokine for which an important role in the immune response against infections and in autoimmune diseases has been demonstrated. Recently, it has been shown that - in addition to mature T cells which are primed in the immune periphery - this cytokine can also be produced by T cells in the thymus, so-called naturally occurring IL-17-producing T cells (nT17 cells). In this study we demonstrate that the generation and activation of nT17 cells in the thymus do not depend on the cytokine IL-6. In addition, nT17 cells are not regulated by IL-2. These properties of nT17 cells significantly differ from induced IL-17-producing T cells primed in the immune periphery (iT17 cells). Given the strong association of IL-17-producing T cells with immune responses against infections and human autoimmune diseases, closer characterization of nT17 cells is warranted., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Experimental autoimmune encephalomyelitis (EAE) is commonly regarded as an animal model of the human disease multiple sclerosis (MS). Pertussis toxin (PTX) is routinely used for EAE induction in mice. Besides opening the blood-brain barrier, it acts as an adjuvant causing strong expansion of antigen-specific cells after coinjection with neuroantigens in IFA. Using an IL-17 ELISPOT assay we developed previously, we investigated the capability of PTX to induce proteolipid protein peptide 139-151(PLPp)-specific Th-17 cells in the immune periphery and in the thymus after coinjection with PLPp/IFA. PTX was found to induce peripheral PLPp-specific Th-17 cells in the draining lymph node and in the spleen, but not in the thymus. Our study indicates a new mechanism by which microbial agents can initiate or maintain autoimmune reactions and supports the growing role in particular for Th-17 cells in organ-specific autoimmune diseases like multiple sclerosis or EAE.

IL-17 is a potent proinflammatory cytokine produced by activated memory T cells. Recent studies in both human autoimmune diseases and in their animal models have indicated that IL-17 rather than IFN-gamma might be the essential T-cell effector cytokine in the T-cell mediated autoimmune process. Since the thymus has a central role in maintaining T-cell self-tolerance and disturbance of thymic self-tolerance is implied in various autoimmune diseases, we here investigated the capability of murine thymocytes to produce IL-17. Our results indicate that thymocytes are a potent source of IL-17 in response to CD3 stimulation and various microbial immune stimuli and thereby show different patterns in the expression of the proinflammatory cytokines IFN-gamma and IL-17. In addition, strong differences between thymocytes and splenocytes were detected. Altered IL-17 production by thymocytes upon contact with foreign pathogens might be a key regulator in the education of adaptive immunity.