The size and condition of the peripheral CD4 T cell population determine the capacity of the immune response. Under homeostatic conditions, the size of the peripheral CD4 T cell population is maintained through turnover and survival. However, the underlying mechanisms remain inadequately understood. Here, we observed a significant decrease in the percentage of CD4 T cells in the periphery following the targeted deletion of the Paxbp1 gene in mouse T cells. In the absence of Paxbp1, naïve CD4 T cells displayed reduced surface interleukin-7 receptor levels and a decreased capacity to respond to survival signals mediated by interleukin-7. In addition, naïve CD4 T cells deficient in Paxbp1 demonstrated impaired T cell antigen receptor signalling, compromised cell cycle entry, decreased proliferation, and increased apoptosis following stimulation, all of which contributed to the reduction in the number of peripheral CD4 T cells. Therefore, our study highlights the indispensable role of Paxbp1 in maintaining peripheral CD4 T cell homeostasis.
Keywords: IL‐7; Paxbp1; TCR; homeostasis; naïve CD4 T cells.
© 2024 John Wiley & Sons Ltd.