Interleukin 12 and CD86 Regulate Th1 and Th2 Development Induced by a Range of Antigen Doses Presented by Peyer's Patch and Spleen Cells.

In this study, we demonstrate the role of interleukin 12 (IL-12), CD80 and CD86 in T helper type 1 (Th1) and Th2 differentiation induced through antigen presentation by Peyer's patch (PP) and spleen (SPL) cells with various doses of antigen. IL-12 was found to be critical for the induction of Th1-type cytokine producing cells, while antigen-dose dependent patterns of differentiation into Th2-type cytokine producing cells were not altered by the blockade of IL-12. Further, the difference in the pattern of Th2-type cytokine producing cell differentiation induced by PP and SPL cells depending on the antigen dosage were preserved in the absence of IL-12.

PAR-2 deficient CD4+ T cells exhibit downregulation of IL-4 and upregulation of IFN-gamma after antigen challenge in mice.

Background: To investigate the functional role of protease activated receptor (PAR) -2 in T lymphocytes, we analyzed TCR-mediated inflammatory cytokine production using PAR-2 deficient (KO) and wild type (WT) mice.

Methods: Production of serum IgE and cytokines by spleen CD4+ T cells was determined in OVA-sensitized and OVA-challenged mice of PAR-2 KO in contrast to WT mice. Phosphorylation of JNK1 and 2 was determined by Western blotting.

A selective novel low-molecular-weight inhibitor of IkappaB kinase-beta (IKK-beta) prevents pulmonary inflammation and shows broad anti-inflammatory activity.

1 Pulmonary inflammatory diseases such as asthma are characterized by chronic, cell-mediated inflammation of the bronchial mucosa. 2 Recruitment and activation of inflammatory cells is orchestrated by a variety of mediators such as cytokines, chemokines, or adhesion molecules, the expression of which is regulated via the transcription factor nuclear factor kappa B (NF-kappaB). 3 NF-kappaB signaling is controlled by the inhibitor of kappa B kinase complex (IKK), a critical catalytic subunit of which is IKK-beta.

The orally available spleen tyrosine kinase inhibitor 2-[7-(3,4-dimethoxyphenyl)-imidazo[1,2-c]pyrimidin-5-ylamino]nicotinamide dihydrochloride (BAY 61-3606) blocks antigen-induced airway inflammation in rodents.

Spleen tyrosine kinase (Syk) tyrosine kinase plays essential roles in receptors for Fc portion of immunoglobulins and B cell receptor complex signaling in various inflammatory cells; therefore, inhibitors of Syk kinase may show potential as antiasthmatic/allergic therapeutics. We identified 2-[7-(3,4-dimethoxyphenyl)-imidazo[1,2-c]pyrimidin-5-ylamino]-nicotinamide dihydrochloride (BAY 61-3606), a potent (Ki = 7.5 nM) and selective inhibitor of Syk kinase.

Antigen presentation by Peyer's patch cells can induce both Th1- and Th2-type responses depending on antigen dosage, but a different cytokine response pattern from that of spleen cells.

The Th1 and Th2 preference induced by cells from the Peyer's patch (PP) and spleen (SPL) with various doses of an antigen was examined. The same splenic T cell receptor-transgenic CD4+ T cells were first incubated with PP or SPL cells in the presence of various doses of an antigen, and the cytokine response was observed after secondary stimulation. A Th2-type pattern was only obtained for primary stimulation at 10 microM of the antigen with PP cells, whereas a Th1 pattern was induced at both higher and lower concentrations.