TCF-7 differentially regulates CD4 T cells mediated alloimmunity

Abstract The transcription factor T Cell Factor-7, encoded by TCF-7, is critical for T cell development. However, the role of TCF-7 on peripheral CD4 T cell-mediated alloimmunity is currently unknown. In this report using a clinically relevant model, we presented novel findings on how TCF-7 regulates CD4 T cell functions, including CD4 T cell activation, phenotype, and effector and central memory formation. We uncovered how TCF-7 regulates chemokine receptors, which are essential for CD4 T cell migration to the site of inflammation. We provide molecular, and transcriptomic evidence that TCF-7 functionally regulates CD4 T cell-mediated apoptosis and cell death, T cell-mediated processes, and proinflammatory and anti-inflammatory cytokine production, differentiation at baseline and after alloactivation. These novel findings represent a step forward to designing a target-specific approach for CD4 T cell-mediated diseases, while enhancing understanding of the molecular mechanism behind the role of CD4 T cells in alloimmunity.