FIG. 7.

Two different NADPH oxidase systems operate during activation of T cells. At early stages after TCR-activation, Ca²⁺-dependent IP3 generation leads to activation of the IP3 receptor on the ER membrane. This causes DUOX1-induced superoxide, which is dismutated into H₂O₂. This acts to promote T cell activation in the early stages. DUOX isoforms may also operate within the endosome. At later stages, the NOX2-based system generates superoxide in a Ca²⁺-independent manner. H₂O₂ generated from these steps may build up and negatively regulate the IP3 pathway through inhibition of SHP-2. This is believed to down-modulate T cell activation. DUOX, dual oxidase; SHP-2.