No abstract

Nippostrongylus brasiliensis (Nb) infection of mice induces IL-4 producing CD4+ T cells which stimulate polyclonal IgE and IgG1 production, providing a model system to study IL-4 action on B cells in vivo. B cell Ia expression and the proportion of IL-2R beta positive B cells were increased in Nb-inoculated mice, and B cells from these mice responded to IL-2 by prompt and marked cell growth. Injection of anti-IL-4 1 day after Nb inoculation substantially inhibited these responses, indicating that they were largely IL-4 dependent. Thus IL-4 acted as a polyclonal B cell activator in vivo and caused B cells to develop into IL-2 responsive cells. Furthermore, injection of IL-2 inhibited IgG1 and IgE production by Nb-inoculated mice. To understand the mechanism of this IL-2-mediated inhibition, we used an in vitro IgG1 and IgE induction system. B cells from Nb-inoculated mice displayed an increase in the capacity of IL-2 to inhibit lipopolysaccharide (LPS) plus IL-4-driven IgE and IgG1 production, indicating that B cells expressing IL-2R beta are highly sensitive to IL-2. This inhibition was principally dependent upon the direct action of IL-2 on B cells. However, partial abolition of IL-2 inhibitory action by anti-IFN-gamma treatment suggested that endogenous IFN-gamma released from IL-2-stimulated cells was also involved in this IL-2-mediated IgE and IgG1 inhibition. Northern blot analysis demonstrated that IL-2 inhibited IL-4 induction of germline and productive C epsilon transcripts in LPS-stimulated B cells. Digestion-circularization polymerase chain reaction analysis revealed IL-2 inhibited IL-4 induction of s mu-s gamma 1 rearrangement in LPS-stimulated B cells.

The total dust concentration and the particle size distribution were determined around die sites of demolition associated with the Great Hanshin-Awaji Earthquake, which occurred on January 17, 1995. The total dust concentrations ranged from 0.20 to 0.23 mg/m(3), being about 1.2 to 2.2 times that in die non-demolition area, and intermediate particles (2.1-11.0μm) made up a large proportion of the dust. The dust concentrations were not influenced by the weather on the day preceding measurement around the sites of demolition of concrete buildings, whereas the values decreased to about half around die sites of demolition of wooden buildings, nearly the same concentration in the control areas, when it had rained on the previous day. The dust concentrations increased compared with that in an average year but to The degree of die upper limit of die environmental standard (1 hr-value<0.20 mg/m(3)) . The dust due to the smoke of Mt. Sakurajima in the surrounding areas accounted for a higher proportion of large particles (<11.0>m) than in the earthquake-devastated area. The concentration of respirable dust (<;7.07>m) in a worker engaged in demolition was 4.0 mg/m(3), being twice the recommended concentration (2 mg/m(3)) of the Japan Society for Occupational Health. It was thus considered that workers should use a respiratory protective device.

SJL mice are known for their poor IgE production upon helminth infection. In this study, we have demonstrated that SJL standard B cells (85% IgM+ or B220+), prepared by complement-mediated T cell lysis, failed to proliferate and to produce IgE and IgG1 in response to LPS plus IL-4 in vitro. This diminished IgE production was restored by anti-IL-12 and enhanced by additional treatment with anti-IL-18, suggesting active suppression by the cells that produce IL-12 and IL-18. Indeed, SJL standard B cells were contaminated with Mac-1+ cells. Therefore, we removed macrophages by passing standard B cells through a Sephadex G-10 column (G10). Resultant cells (95% IgM+), designated as G10-B cells, responded to LPS and IL-4 by their proliferation and differentiation. G-10 treatment markedly diminished the proportion of B220− cells and Mac-1+ cells in SJL standard B cells. Furthermore, addition of SJL B220− cells dose dependently and MHC independently inhibited LPS plus IL-4-induced B cell growth and IgE production in SJL and BALB/c B cells. B220− cells in SJL standard B cells contained Mac-1+ cells (51%) and Fas ligand+ CD4−CD8− double-negative CD3intIL-2Rβ+ T cells (26%). Thus, IL-12 and IL-18 produced by LPS-stimulated Mac-1+ cells stimulate this unique subpopulation of T cells to produce IFN-γ, which in combination with Fas ligand, inhibits IgE production from the B cells. Our present results indicate that Mac-1+ cells and double-negative CD3intIL-2Rβ+ T cells, uniquely abundant in the spleens of SJL mice, inhibit IgE production, indicating their new role in IgE response.