NF-E2-related factor 2 (Nrf2), known to protect against reactive oxygen species (ROS), recently emerged to resolve acute inflammatory responses in activated macrophages. Consequently, disruption of Nrf2 promotes a pro-inflammatory macrophage phenotype. In the current study, we addressed the impact of this macrophage phenotype on CD8+ T cell activation by using an antigen-driven co-culture model consistent of Nrf2-/- and Nrf2+/+ bone marrow derived macrophages (BMDMΦ) and transgenic OT-1 CD8+ T cells. OT-1 CD8+ T cells encode a T cell receptor that specifically recognizes MHCI-presented OVA(257-264) peptide, thereby causing a downstream T cell activation. Interestingly, co-culture of OVA(257-264)-pulsed Nrf2-/- BMDMΦ with transgenic OT-1 CD8+ T cells attenuated CD8+ T cell activation, proliferation, and cytotoxic function, compared to Nrf2+/+ BMDMΦ.Since the provision of low molecular thiols such as glutathione (GSH) or cysteine (Cys) by macrophages limits antigen-driven CD8+ T cell activation, we quantified the amount of intracellular and extracellular GSH and Cys in both co-cultures. Indeed, GSH levels were strongly decreased in Nrf2-/- co-cultures compared to wildtype counterparts. Supplementation of thiols in Nrf2-/- co-cultures via addition of glutathione ester, N-acetylcysteine, β-mercaptoethanol, or cysteine itself restored T cell proliferation as well as cytotoxicity by increasing intracellular GSH. Mechanistically, we identified two potential Nrf2-regulated genes involved in thiol synthesis in BMDMΦ: the cystine transporter subunit xCT and the modulatory subunit of the GSH synthesizing enzyme γ-GCS (GCLM). Pharmacological inhibition of γ-GCS-dependent GSH synthesis as well as knockdown of the cystine importer xCT in Nrf2+/+ BMDMΦ mimicked the effect of Nrf2-/- BMDMΦ on CD8+ T cell function. Our findings demonstrate, that reduced levels of GCLM as well as xCT in Nrf2-/- BMDMΦ limit GSH availability, thereby inhibiting antigen-induced CD8+ T cell function.