Critical role of regulatory T cells in Th17-mediated minor antigen-disparate rejection

Th17-mediated immune responses have been recently identified as novel pathogenic mechanisms in a variety of conditions; however, their importance in allograft rejection processes is still debated. In this paper, we searched for MHC or minor Ag disparate models of skin graft rejection in which Th17 immune responses might be involved. We found that T cell-derived IL-17 is critical for spontaneous rejection of minor but not major Ag-mismatched skin grafts. IL-17 neutralization was associated with a lack of neutrophil infiltration and neutrophil depletion delayed rejection, suggesting neutrophils as an effector mechanism downstream of Th17 cells. Regulatory T cells (Tregs) appeared to be involved in Th17 reactivity. We found that in vivo Treg depletion prevented IL-17 production by recipient T cells. An adoptive cotransfer of Tregs with naive monospecific antidonor T cells in lymphopenic hosts biased the immune response toward Th17. Finally, we observed that IL-6 was central for balancing Tregs and Th17 cells as demonstrated by the prevention of Th17 differentiation, the enhanced Treg/Th17 ratio, and a net impact of rejection blockade in the absence of IL-6. In conclusion, the ability of Tregs to promote the Th17/neutrophil-mediated pathway of rejection that we have described should be considered as a potential drawback of Treg-based cell therapy.

An ERP study of major-minor classification in melodies

COMPOSERS COMMONLY USE MAJOR OR MINOR SCALES to create different moods in music.Nonmusicians show poor discrimination and classification of this musical dimension; however, they can perform these tasks if the decision is phrased as happy vs. sad.We created pairs of melodies identical except for mode; the first major or minor third or sixth was the critical note that distinguished major from minor mode. Musicians and nonmusicians judged each melody as major vs. minor or happy vs. sad.We collected ERP waveforms, triggered to the onset of the critical note. Musicians showed a late positive component (P3) to the critical note only for the minor melodies, and in both tasks.Nonmusicians could adequately classify the melodies as happy or sad but showed little evidence of processing the critical information. Major appears to be the default mode in music, and musicians and nonmusicians apparently process mode differently.