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.

Psychological Real Estate: Fractured Female Identity in the Victorian Novel

"Psychological Real Estate: Fractured Female Identity in the Victorian Novel" examines the use of domestic space in three Victorian novels, Charlotte Bronte's Jane Eyre (1847), Mary Elizabeth Braddon's Lady Audley's Secret (1862), and George Eliot's Middlemarch (1871-2). Because Victorian gender identity was conceived of in spatial terms, this thesis explores how the three female authors use complicated domestic environments to engage the problem of conventional Victorian femininity. In the Victorian mindset, a woman's place is confined to the home, or private sphere; however, even the private sphere is intruded upon by public spaces. Expected to conform to the Victorian formulation of femininity in public spaces within the home, women had only their private spaces to cultivate the unique, individualistic aspects of their selves. This thesis explores the ways in which the female protagonists negotiate these gender encoded spaces to argue that because Victorian women had to maintain separate and often disparate identities within domestic space, their identities became problematically fractured. Additionally, in each of these texts, the authors use the failure or loss of the estate, the structure which rigidly upholds the gendered binaries, to expose the harm such fracturing identity formulation caused for Victorian society as a whole. This thesis concludes by examining the final residences of the female characters and arguing that the authors use these final private spaces to assert more feminist re-envisionings of their society's construction of femininity.