Survival and Developmental Progression of Unselected Thymocytes in the Absence of the T‐Cell Adaptor Gads

• DOI: 10.1002/eji.202451000
• Publication Date: 2025-02-27T13:23:45Z
• Authors: Rose Shalah; Manal Marzouk; Enas Hallumi; Naama Klopstock; Deborah Yablonski
• Keywords: Thymocyte; Negative selection; Ex vivo

Thymocyte β-selection and positive-selection depend on TCR signaling via the immune adaptors SLP-76 LAT. Gads bridges recruitment of to LAT, yet is not required for maturation single positive (SP) thymocytes. To illuminate this paradox, we performed tamoxifen-induced ablation (GadsiKO), accompanied by expression tdTomato, compared development Gads-expressing (Tom-) Gads-ablated (Tom+) thymocytes within same mouse. GadsiKO exhibited impaired β- positive-selection, δ-selection was affected. While susceptible apoptosis ex vivo, marked accumulation self-MHC nonresponding (CD5-) DP suggested possibility death neglect in situ. Further supporting notion, CD5lo reduced situ CD8-induced vivo. Most CD4 SP were positively selected, a distinct population unselected (CD5- TCRβneg/low CCR7lo CD24hi) seen only absence Gads. This did include Treg or TCRγδ subsets; rather, it encompassed CD44lo CD25+ cells, resembling pre-β-selection Our results suggest that promotes passage through key TCR-driven developmental checkpoints while repressing progression DN