Functional expression of NOD2 in freshly isolated human peripheral blood γδ T cells.

γδ T cells play an important role in anti-infective immunity. The major subset of human γδ T cells selectively recognizes phosphorylated bacterial metabolites of the isoprenoid biosynthesis pathway, so-called phosphoantigens. The activation of γδ T cells is modulated by functionally expressed innate immune receptors, notably Toll-like receptor 2 and 3. It was also reported that in vitro expanded γδ T cells respond to muramyl dipeptide (MDP), the minimal peptidoglycan motif activating the nucleotide-binding oligomerization domain containing 2 (NOD2) receptor, although it is unknown whether ex vivo isolated human γδ T cells express functional NOD2. Here, we report that freshly isolated, highly purified peripheral blood γδ T cells express NOD2 mRNA and detectable amounts of NOD2 protein. The biologically active MDP L-D isomer but not the inactive D-D isomer augmented the interferon-γ (IFN-γ) secretion in phosphoantigen-stimulated peripheral blood mononuclear cells. Moreover, a moderate but reproducible and statistically significant increase in IFN-γ secretion was also observed when highly purified peripheral blood γδ T cells were activated by T cell receptor cross-linking in the presence of MDP. Taken together, our results indicate that in addition to the T cell receptor and Toll-like receptors, circulating human γδ T cells express NOD2 as a third class of pattern recognition receptor for sensing bacterial products.

Allergen IgE-isotype-specific suppression by maternally derived monoclonal anti-IgG-idiotype.

BACKGROUND: The dramatic increase of IgE-mediated allergic diseases in western countries demonstrates the urgent need for new therapeutic or prophylactic approaches. In mice, a prophylactic long-lasting allergen-specific suppression of IgE responsiveness is induced by maternal IgG antibodies to allergens like ovalbumin, phospholipase A(2) (bvPLA(2)) or ovomucoid. As neonatal application or maternally derived pathogen-reactive antibodies (idiotypes) as well as corresponding anti-idiotypes can induce anti-microbial protection, we probed the transgenerational IgE-suppressive mechanism with a syngeneic monoclonal anti-idiotypic antibody. METHODS: The monoclonal bee-venom-phospholipase A(2) (bvPLA(2))-reactive IgG antibody MS613 (idiotype) or the corresponding syngeneic anti-idiotype II/2-19 were injected during the first 2 days postpartum to the dams. Immunization of offspring with minute doses of IgE-inducing bvPLA(2) was started at an adult age of 3(1/2) months. RESULTS: The postnatal transfer of the anti-bvPLA(2) idiotype MS613 or the corresponding anti-idiotype II/2-19 induced long-lasting allergen-specific IgE suppression in a dose-dependent manner, while the IgG response to the allergen developed normally. Quantitatively, the anti-idiotype was more effective than idiotype. Molecular modeling of the idiotype-anti-idiotype complex and its comparison with the bvPLA(2) structure revealed that the anti-idiotype does not mimic bvPLA(2) epitopes and thus can not be regarded as an internal image antibody and, consequently, does not function as a surrogate antigen. CONCLUSIONS: Idiotypic network reactivity is at least one major factor for induction of transgenerational IgE suppression by maternal IgG antibodies. If applicable to humans, these data suggest the possibility of a prophylactic and possibly therapeutic treatment of IgE-mediated allergic diseases with anti-idiotypic antibodies.

Acoustic scattering by a modified Werner method

A modified integral Werner method is used to calculate pressure scattered by an axisymmetric body immersed in a perfect and compressible fluid subject to a harmonic acoustic field. This integral representation is built as the sum of a potential of a simple layer and a potential of volume. It is equivalent to the exterior Helmholtz problem with Neumann boundary condition for all real wave numbers of the incident acoustic field. For elastic structure scattering problems, the modified Werner method is coupled with an elastodynamic integral formulation in order to account for the elastic contribution of the displacement field at the fluid/structure interface. The resulting system of integral equations is solved by the collocation method with a quadratic interpolation. The introduction of a weighting factor in the modified Werner method decreases the number of volume elements necessary for a good convergence of results. This approach becomes very competitive when it is compared with other integral methods that are valid for all wave numbers. A numerical comparison with an experiment on a tungsten carbide end-capped cylinder allows a glimpse of the interesting possibilities for using the coupling of the modified Werner method and the integral elastodynamic equation used in this research.