The Role of Cdc42 in T cell Polarity, development and immune responses

Abstract

This study explores the role of Cdc42 in T cell polarity, specifically focusing oncell-cell contact, chemokine interactions, and ECM adhesion. Using SEM toobserve thymopoiesis, we observed dynamic changes in microvilli morphology,with elongation during the transition from double-positive to single-positivestages. Additionally, Cdc42-deficient CD4+ T cells exhibited developmental defects, characterized by reduced CD4+ and CD8+ populations in the thymus andlymph nodes. In vitro SEM revealed a developmental block in CDC42 knockout CD4single-positive cells, marked by shorter and fewer microvilli and reduced cell mass and size. Furthermore,the developmental defects were associated with a proliferation defect andincreased apoptosis, highlighting the critical role of Cdc42 in regulatingsurvival and proliferation signals throughout multiple stages of T celldevelopment. Our findings emphasize the importance of Cdc42 in maintaining homeostasisin CD4+ T cells, as its absence may disrupt T cell survival. Additionally,OVA-specific transgenic CD4+ T cells lacking Cdc42 exhibited impaired F-actinand immunological synapse polarization upon exposure to OVA-presenting APCs,both in vitro and in vivo. Also we demonstrates the essential role of Cdc42 inT cell migration and adhesion, contributing to the impaired homing of mature Tcells to lymph nodes. These findings provide valuable insights into themultifaceted functions of CdC42 in T cell development and immune responses.