It was observed in vitro and in vivo that both interferon (IFN)-gamma and interleukin (IL)-12 can promote the development of T helper type 1 (TH1) cells. Since IL-12 was shown to be a costimulator for the production of IFN-gamma by T or natural killer (NK) cells, IL-12 might play only an indirect role in TH1 differentiation by providing IFN-gamma which represents the essential differentiation factor. Using anti-CD3 monoclonal antibody (mAb) for activation of naive CD4+ T cells in the absence of accessory cells we could demonstrate that costimulation by IFN-gamma alone results only in marginal TH1 development. Similarly, IL-12 in the absence of IFN-gamma is only a poor costimulator for inducing differentiation towards the TH1 phenotype. Our data indicate that both cytokines are required to allow optimal TH1 development and that IL-12 has a dual role, it promotes differentiation by direct costimulation of the T cells and also enhances the production of IFN-gamma which serves as a second costimulator by an autocrine mechanism. Another cytokine that was reported to favor TH1 differentiation in certain experimental systems is transforming growth factor (TGF)-beta. With naive CD4+ T cells employed in this study TGF-beta strongly inhibited the production of IFN-gamma triggered by IL-12 as well as the IL-12-induced TH1 development. When TGF-beta was combined with anti-IFN-gamma mAb for neutralization of endogenous IFN-gamma the TH1-inducing capacity of IL-12 was completely suppressed.

Activation of naive dense CD4+ T cells by plate-bound anti-CD3 antibodies favors the development of Th1 cells which, upon re-stimulation, produce significant amounts of IFN-gamma but no IL-4. However, co-activation of such naive T cells in the presence of IgE [anti-dinitrophenyl (DNP)]-loaded bone marrow-derived mast cells (BMMC) on plates coated with anti-CD3 antibodies and DNP-BSA led to the development of IL-4-producing Th2 cells. The same result could be observed if irradiated (800 rad) BMMC were applied as co-stimulators. Moreover, BMMC could be replaced by the supernatant of IgE-activated BMMC suggesting that a soluble mediator, presumably IL-4, was responsible for this effect. This assumption was substantiated using neutralizing anti-IL-4 antibodies which abolished the BMMC-mediated Th2 development in all cases. Addition of IL-12, a cytokine that was shown to antagonize the Th2-promoting effect of IL-4 in vivo, could not inhibit the development of IL-4-producing T cells, but gave rise to a T cell population which produced relatively high amounts of IL-4 and IFN-gamma. Since BMMC represent the in vitro equivalent of mucosal mast cells these data suggest that IgE-activated mucosal mast cells can bias an emerging T cell dependent immune response towards a Th2 dominated reaction by the initial production of IL-4.

No abstract

Dense CD4+ T cells isolated from naive mice produce only trace amounts of IL-9 when stimulated by immobilized anti-CD3 in combination with anti-CD28 Abs. In this situation, IL-9 production is significantly stimulated by TGF-beta and further enhanced by the addition of IL-4, which, by itself, has only a minimal influence. IFN-gamma was found to inhibit the enhancing effect of IL-4. However, increasing amounts of IL-4 in the presence of a constant concentration of IFN-gamma could overcome the inhibitory activity of IFN-gamma. The application of CD4+ T cells isolated from IL-2 knockout mice unequivocally revealed that IL-2 is essential for the production of IL-9 by T cells. In addition, the use of T cells from IL-4 knockout mice elucidated that the basic (IL-2 + TGF-beta) mediated IL-9 production is independent of IL-4. Therefore, our results demonstrate that optimal IL-9 production of naive dense CD4+ T cells is positively regulated at different levels: 1) by IL-2, which is essential for IL-9 secretion; 2) followed by TGF-beta, which promotes a considerable increase in IL-9 production above the level induced by IL-2; and 3) finally, by IL-4, which requires the presence of IL-2 and TGF-beta to strongly enhance the production of IL-9. IFN-gamma inhibits the production of IL-9 mainly at the level of IL-4 by neutralizing the effect of this cytokine.

Am 26. August 2004 hat ein tragischer Verkehrsunfall eines Tankfahrzeuges auf der Wiehltalbrücke zu dessen Absturz von der Brücke und zu erheblicher Brandeinwirkung auf den Stahlüberbau im ersten Brückenfeld geführt.Der Beitrag schildert die Sofortmaßnahme zur Sicherung der Brücke, provisorische Verstärkungen zur schnellen Wiederaufnahme des Autobahnverkehrs und die endgültige Instandsetzung zur Wiederherstellung des ursprünglichen Brückenzustandes.Charakteristisch für die Robustheit der Stahlkonstruktion gegenüber Brand ist, daß trotz Flammtemperaturen um 1200 °C die Objekttemperatur nur etwa 500 °C erreichte, so daß die Schäden in Grenzen blieben.Die darauf schließenden Werkstoffbefunde wurden durch einen rechnerischen Nachweis mit Naturbrand bestätigt.