TCDD attenuates EAE through induction of FasL on B cells and inhibition of IgG production.

Previously we demonstrated that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suppressed experimental autoimmune encephalomyelitis (EAE), a model to study multiple sclerosis (MS), through induction of regulatory T cells (Tregs) and suppression of effector T cell function in the spleen. Since B cells and specifically regulatory B cells (Bregs) have been shown to be so critical in the pathology associated with EAE and MS, we wanted to determine whether TCDD could also induce Bregs. We specifically hypothesized that a Fas ligand (FasL)+ Breg population would be induced by TCDD in EAE thereby triggering apoptosis in Fas-expressing effector T cells as one mechanism to account for inhibition of T cell function by TCDD. TCDD (0.1-2.5 µg/kg/day administered orally for 12 days) modestly increased the percentage of FasL + B cells in the spleen and spinal cord in TCDD-treated EAE mice. However, we did not detect significant increases in percentages of FasL + B cells using TCDD in vitro in mouse splenocytes or human peripheral blood mononuclear cells (PBMCs). Part of the modest effect by TCDD was likely related to the localized expression of FasL; for instance, in the spleen, FasL was more highly expressed by IgMhiIgDlo marginal zone (MZ) B cells, but IgMloIgDhi follicular (FO) B cells were more responsive to TCDD. Consistent with our observation of modest upregulation of FasL, we also observed modest changes in mitochondrial membrane potential in T cells co-cultured with isolated total B cells or IgM-depleted (i.e., FO-enriched) B cells from TCDD-treated EAE mice. These data suggest that while small microenvironments of apoptosis might be occurring in T cells in response to TCDD-treated B cells, it is not a major mechanism by which T cell function is compromised by TCDD in EAE. TCDD did robustly suppress IgG production systemically and in spleen and spinal cord B cells at end stage disease. Thus, these studies show that TCDD's primary effect on B cells in EAE is compromised IgG production but not FasL + Breg induction.

Auditory perception of motor vehicle travel paths.

OBJECTIVE: These experiments address concerns that motor vehicles in electric engine mode are so quiet that they pose a risk to pedestrians, especially those with visual impairments. BACKGROUND: The "quiet car" issue has focused on hybrid and electric vehicles, although it also applies to internal combustion engine vehicles. Previous research has focused on detectability of vehicles, mostly in quiet settings. Instead, we focused on the functional ability to perceive vehicle motion paths. METHOD: Participants judged whether simulated vehicles were traveling straight or turning, with emphasis on the impact of background traffic sound. RESULTS: In quiet, listeners made the straight-or-turn judgment soon enough in the vehicle's path to be useful for deciding whether to start crossing the street. This judgment is based largely on sound level cues rather than the spatial direction of the vehicle. With even moderate background traffic sound, the ability to tell straight from turn paths is severely compromised. The signal-to-noise ratio needed for the straight-or-turn judgment is much higher than that needed to detect a vehicle. CONCLUSION: Although a requirement for a minimum vehicle sound level might enhance detection of vehicles in quiet settings, it is unlikely that this requirement would contribute to pedestrian awareness of vehicle movements in typical traffic settings with many vehicles present. APPLICATION: The findings are relevant to deliberations by government agencies and automobile manufacturers about standards for minimum automobile sounds and, more generally, for solutions to pedestrians' needs for information about traffic, especially for pedestrians with sensory impairments.