EIF2AK4 and chronic obstructive pulmonary disease: Furthermore, compared to HS, CD8+ T cells from COPD airways downregulated the functional pathways, including cell-cell adhesion, T cell migration, defense response, IL-2 production, and TCR signaling; conversely, they upregulated the T cell exhaustion-associated pathways, such as influenza infection, PD-1 signaling, IFN-γ signaling, and response of EIF2AK4 (GCN2) to amino acid deficiency (Figure 2D).