Person:
Kaskow, Belinda

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Kaskow

First Name

Belinda

Name

Kaskow, Belinda

Filters

2017 - 20182

Settings

Author's Publications: search.filters.isAuthorOfPublication.9bd93474-185f-484e-9e90-ecfae469c153

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Publication
    Optimizing human Treg immunotherapy by Treg subset selection and E-selectin ligand expression
    (Nature Publishing Group UK, 2018) Donnelly, Conor; Dykstra, Brad; Mondal, Nandini; Huang, Junning; Kaskow, Belinda; Griffin, Russell; Sackstein, Robert; Baecher-Allan, Clare
    While human Tregs hold immense promise for immunotherapy, their biologic variability poses challenges for clinical use. Here, we examined clinically-relevant activities of defined subsets of freshly-isolated and culture-expanded human PBMC-derived Tregs. Unlike highly suppressive but plastic memory Tregs (memTreg), naïve Tregs (nvTreg) exhibited the greatest proliferation, suppressive capacity after stimulation, and Treg lineage fidelity. Yet, unlike memTregs, nvTregs lack Fucosyltransferase VII and display low sLeX expression, with concomitant poor homing capacity. In vitro nvTreg expansion augmented their suppressive function, but did not alter the nvTreg sLeX-l ° w glycome. However, exofucosylation of the nvTreg surface yielded high sLeX expression, promoting endothelial adhesion and enhanced inhibition of xenogeneic aGVHD. These data indicate that the immature Treg glycome is under unique regulation and that adult PBMCs can be an ideal source of autologous-derived therapeutic Tregs, provided that subset selection and glycan engineering are engaged to optimize both their immunomodulation and tropism for inflammatory sites.
  • Thumbnail Image
    Publication
    MS AHI1 genetic risk promotes IFNγ+ CD4+ T cells
    (Lippincott Williams & Wilkins, 2017) Kaskow, Belinda; Buttrick, Thomas S.; Klein, Hans-Ulrich; White, Charles; Bourgeois, Justin R.; Ferland, Russell J.; Patsopoulos, Nikolaos; Bradshaw, Elizabeth M.; De Jager, Philip; Elyaman, Wassim
    Objective: To study the influence of the Abelson helper integration site 1 (AHI1) locus associated with MS susceptibility on CD4+ T cell function. Methods: We characterized the chromatin state of T cells in the MS-associated AHI1 linkage disequilibrium (LD) block. The expression and the role of the AHI1 variant were examined in T cells from genotyped healthy subjects who were recruited from the PhenoGenetic Project, and the function of AHI1 was explored using T cells from Ahi1 knockout mice. Results: Chromatin state analysis reveals that the LD block containing rs4896153, which is robustly associated with MS susceptibility (odds ratio 1.15, p = 1.65 × 10−13), overlaps with strong enhancer regions that are present in human naive and memory CD4+ T cells. Relative to the rs4896153A protective allele, the rs4896153T susceptibility allele is associated with decreased AHI1 mRNA expression, specifically in naive CD4+ T cells (p = 1.73 × 10−74, n = 213), and we replicate this effect in an independent set of subjects (p = 2.5 × 10−9, n = 32). Functional studies then showed that the rs4896153T risk variant and the subsequent decreased AHI1 expression were associated with reduced CD4+ T cell proliferation and a specific differentiation into interferon gamma (IFNγ)–positive T cells when compared with the protective rs4896153A allele. This T cell phenotype was also observed in murine CD4+ T cells with genetic deletion of Ahi1. Conclusions: Our findings suggest that the effect of the AHI1 genetic risk for MS is mediated, in part, by enhancing the development of proinflammatory IFNγ+ T cells that have previously been implicated in MS and its mouse models.