LCK deficiency in CD8 T cells leads to reduced proliferation and increased effector T-cell formation in mice [Bulk RNA-seq]

While its developmental role is well established, its functions in peripheral T-cell responses remain poorly defined. Here, we investigated the responses of wild-type and LCK-deficient TCR-transgenic OT-I T cells across two infection models and an autoimmune diabetes model.

LCK-deficient T cells exhibited reduced antigen-induced proliferation but, paradoxically, displayed enhanced effector differentiation in vivo. This phenotype likely reflects dysregulation of specific TCR signaling pathways, as LCK was more critical for ERK and NFAT activation than for NFκB, AP-1, or AKT/mTOR signaling. T cells deficient in a related kinase FYN also showed a slight increase in effector cell formation, suggesting that effector differentiation is regulated by their combined activity rather than distinct non-redundant roles.