Figure 1.

ROS modulate several aspects of T cell-mediated immunity downstream of TCR stimulation. (A) Following activation, signaling through the TCR stimulates the mitochondria to produce ROS, which in turn promote continued TCR signaling. The level of activation-induced ROS within the cell also critically affects the downstream functions of T cell proliferation, differentiation, and survival. Therefore, the modulation of ROS levels by cellular antioxidant pathways (e.g., GSH; Nrf2-Keap1-Cul3 trimeric complex) is crucial in maintaining proper T cell-mediated immunity. GSH regulates ROS levels by directly reducing free radicals encountered in the cytoplasm. In contrast, the Nrf2-Keap1-Cul3 trimeric complex disassociates upon sensing high levels of cellular ROS, allowing Nrf2 to enter the nucleus and activate the ARE-containing genes. (B) If cellular antioxidant pathways are dysregulated or mutated, cellular ROS levels will not be properly controlled. Therefore, high levels of ROS after T cell activation can lead to the development of several T cell-mediated autoimmune diseases and cancer.

APC, antigen presenting cell; MHC, major histocompatibility complex.