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- W2005070909 abstract "<h3>Abstract</h3> An important paradigm in improving allogeneic hematopoietic stem cell transplantations (allo-HSCTs) is the prevention of graft-vs-host disease (GVHD) while preserving the beneficial graft-vs-leukemia (GVL) activity of donor T cells. From an observational clinical study of 35 adult allo-HSCT recipients, we identified a CD4+/CD8+ double positive T cell (DPT) population, not present in healthy graft tissue, that arises early after transplant and is predictive of ≥ grade 2 GVHD. To investigate this DPT population, we utilized an established xenogeneic transplant model that allowed us to directly investigate human DPTs. Transcriptional, metabolic, and phenotypical analysis revealed DPTs to be highly inflammatory population, distinct from single-positive CD4 and CD8 T cells that display no signs of exhaustion. The origin of DPTs was found to be antigen stimulated CD8 T cells that gained the expression of the CD4 lineage master transcription factor THPOK at both the transcriptional and protein levels. We also reveal that DPTs, isolated from xeno-GVHD mice, were sufficient to mediate xeno-GVHD pathology when re-transplanted into a naive mouse while CD4 and CD8 T cells from the same xeno-GVHD mice were not sufficient. To determine their role in mediating GVL activity, isolated DPTs were transplanted into mice challenged with two different human B-ALL malignancies. We observed that while isolated CD4 and CD8 T cells were able to extend survival, the DPT population had no survival benefit despite their inflammatory profile. Overall, these studies highlight human DPTs as an inflammatory T cell population biased toward GVHD pathology and with limited GVL activity. <h3>One Sentence Summary</h3> We reveal that human CD4+/CD8+ T cells are highly inflammatory, transcriptionally, and metabolically distinct and sufficient to mediate GVHD pathology." @default.
- W2005070909 created "2016-06-24" @default.
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- W2005070909 date "1999-12-01" @default.
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- W2005070909 title "Methodologic issues in assessing risk factors for epilepsy in an epidemiologic study in India" @default.
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- W2005070909 doi "https://doi.org/10.1212/wnl.53.9.2058" @default.
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