Although several studies have focused on allergic sensitization by dendritic cells, to date it is still open under which conditions these antigen-presenting cells are able to induce an allergic immune response. Our study reveals that BMDCs pulsed with LPS-free ovalbumine did not induce allergic disease. However, when BMDCs were activated with low-dose LPS during pulsing with allergen, these cells expressed an inflammatory set of cytokines and co-stimulatory molecules like CD86 and OX40L. Moreover, activated cells were able to prime mice for massive eosinophilic inflammation of the lung, airway hyper-reactivity, IgE production and production of Th2 cytokines by lymphocytes. Blocking experiments showed that expression of OX40L is not involved in induction of Th2 response. Interestingly, BMDCs that were activated with high dose of LPS lose their Th2-sensitizing capacity. Instead these cells induce a Th17 type immune response. We conclude that presentation of allergen by dendritic cells generated with GMCSF is not sufficient to lead to induction of allergic immune response. Further activation of BMDCs is required to prime mice for allergic immune response. In this study, we show that LPS is a suitable stimulus. However, when cells were activated with high dose LPS they tended to induce a Th17 response. Several animal studies have shown that airway sensitization could be achieved by priming mice with allergen-pulsed dendritic cells. [1][2][3] Lambrecht et al. 2 have shown that these antigen-presenting cells are critically involved in both sensitization phase and in ongoing allergic immune response. 2,4 However, in all of these studies ovalbumine preparations were used that were contaminated with LPS. There is some evidence from the literature that a TLR-mediated signal is required for effective induction of Th2 immunity. 5,6 In particular, stimulation via TLR4 seems to be a suitable stimulus as shown for example by Eisenbarth et al. 7 These authors showed that treatment with ovalbumine via the airways is not sufficient to sensitize mice. Only when low doses lipopolysaccharide were mixed to OVA, mice were sensitized towards the allergen. 7 On the basis of this observation Nigo et al. 8 have shown that allergy-promoting activity of low-dose LPS led to activation of mast cells via TLR4. Moreover, a recent publication of Hammad et al. 9 showed that LPS activation of epithelia cells has a significant impact on allergic sensitization towards house dust mite allergens. From these experiments the question arises, whether direct activation of DCs with LPS is sufficient or an LPSinduced cytokine milieu due to activation of mast cells and/or airway epithelium is required to arm these cells for sensitization of mice. As there is some evidence that GMCSF is involved in induction of Th2 response in vivo the possibility must be considered that Th2 induction could be generally attributed to GMCSF-generated dendritic cells. 10,11 Despite several years of research, the question still remains, which phenotype BMDCs must acquire to indu...

Our results suggest that induction of a LPS-tolerant state in antigen-presenting cells (APCs) may contribute to the protective effect of a farming environment. TLR2 agonists similar to those appearing in cowshed dust extracts, such as our synthetic LPGerD, lead to the ignorance of the LPS stimulus, which is important for the activation of APCs to mount a Th2 immune response. This substance might be a promising candidate for allergy-preventive treatments as LPGerD had only low pro-inflammatory characteristics.

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Mononuclear blood cells from patients with different types of leukemia, and from controls as well as cells from established lymphoblastic cell lines were analyzed with respect to terminal transferase (TdT) activity and T-cell growth factor (TCGF; Interleukin 2, IL-2), to determine the significance of TCGF production and response as functional markers for human leukemias. The data obtained so far suggest that the aberrant proliferation and lack of maturation observed in these leukemias may be associated with or be the result of a break-down in cellular-mediated control of proliferation.

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