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Y-Box Binding Proteins regulate CD8+ T cell differentiation and function

  • Author(s): Mamroth, Max Tyler
  • Advisor(s): Chang, John T
  • et al.
Abstract

CD8+ T cells are important for pathogen clearance and have many intrinsic and extrinsic factors that can determine how they differentiate into effector and memory cells. The Y-box binding protein (YBX) family of genes have been identified as potential regulators of CD8+ T cell differentiation as early as the first division (Kakaradov et al. 2017). Previous studies have shown that YBX1 and YBX3 affect various cellular pathways and functions; however, none have focused on YBX genes affecting CD8+ T cell differentiation and function. To address this gap in knowledge, this thesis investigated the effects on CD8+ T cell differentiation at early and late time points in an acute infection model using a shRNA approach. To do this, we validated retroviral shRNAs that knocked down YBX1 and YBX3, and a control non-targeting retroviral construct. Activated P14 CD45.1 and CD45.1.2 CD8+ T cells were transduced with targeting and non-targeting retroviruses, respectively, and adoptively transferred into recipient mice that were subsequently infected with Lymphocytic Choriomeningitis Virus (LCMV) Armstrong. Seven days and thirty days after infection, mice were sacrificed, and spleen and small intestine tissue were analyzed using flow cytometry. Relative to the non targeting control-transduced cells, cells knocked down for YBX1 and YBX3 expression exhibited reduced CD8+ TE and CD8+ TCM populations. Knock down of YBX1 and YBX3 expression also resulted in an increase of CD8+ TRM cells within the small intestine, and an increase of circulating TEM cells and cytokine-producing cells.

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