CD4⁺ CAR T cells are responsible for CAR-associated GVHD. (A) Survival curves and (B) percent weight change of mice receiving DLI on day 2 following syngeneic or allo-BMT into leukemia-bearing mice. DLI consisted of sorted CD4 or CD8 CAR T cells, with the following groups: B6 → C3h.sw CD4⁺ CAR (red), B6 → C3h.sw CD8⁺ CAR (purple), B6 → C3h.sw mock (gray), B6 → B6 CD4⁺ CAR (blue), B6 → B6 CD8⁺ CAR (green), and B6 → B6 mock (black). Data are representative from 2 separate experiments. (C) CD4⁺ and CD8⁺ T cells were isolated from wild-type (WT) B6 or IL-6^−/− donors. Cells were expanded (mock) or expanded and CD19-CAR transduced (CAR), and co-cultured for 16 hours with CD19⁺ tumor (E2a:PBX) or CD19⁻ tumor (EL4). IL-6 levels were measured on supernatant by IL-6 Quantikine ELISA. *P < .05.