(A) Heatmap indicating differential expression of cytotoxic T, Th17, and Th1 cell markers between CD4⁺ and CD8⁺ skin-infiltrating and splenic T cells. Data show 2 or 3 biological replicates. (B) Gene set enrichment analysis (GSEA) plots comparing gene signatures of skin-infiltrating with splenic CD4⁺ T cells based upon the hypoxia signature generated by comparing triple prolyl-hydroxylase–knockout (PHD-KO) CD4⁺ with WT CD4⁺ T cells (17). (C) GSEA plots comparing gene signatures of skin-infiltrating with splenic CD8⁺ T cells based upon the hypoxia signature generated by comparing VHL tumor suppressor KO CD8⁺ T cells with lymphocytic choriomeningitis virus–specific P14 T cell receptor transgenic CD8⁺ T cells taken from virally infected mice (9). (D and E) Representative data and summary of HIF1α staining of splenic versus skin-infiltrating CD4⁺ and CD8⁺ T cells isolated from the skin of MRL/lpr mice 20 to 22 weeks old. (F) Pimonidazole staining of splenic vs. skin-infiltrating CD4⁺and CD8⁺ T cells isolated from the skin of MRL/lpr mice 20 to 22 weeks old. Representative of 2 experiments, n = 6–7 animals per group. (G and H) IF images of MRL/lpr diseased skin stained for HIF1α (G) or isotype control (H) (magenta), CD4 (blue), and CD8 (yellow). White arrowheads indicate HIF-1–expressing CD4⁺ or CD8⁺ T cells. Representative of 7 total sections from 2 mice (see Supplemental Figure 2). Data shown are mean ± SEM. Statistical analysis by 2-tailed paired Student’s t test (E and F). ****P < 0.0001. EPI, epidermis; SG, sebaceous gland; HF, hair follicle.