Figure 8.

CTL treatment paradoxically increases LSCs in a humanized CML model. HLA-A2tg CML mice 19 d after transplantation were either left untreated (Ø, n = 5) or treated with BCR/ABL b3a2 junction peptide-specific HLA-A2tg CD8⁺ T cells (+b3a2-CTLs, n = 4). In a similar, independent experiment, mice were left untreated (Ø, n = 8) or treated with HIV SL9 peptide-specific HLA-A2tg CD8⁺ T cells (+SL9-CTLs, n = 6). 1 d later, mice were bled and sacrificed for analysis. (A) Numbers of BCR/ABL-GFP⁺ granulocytes/µl blood before and 1 d after adoptive transfer of b3a2-CTLs. (B) BM was lineage depleted and analyzed by FACS for the expression of c-kit and Sca-1 after adoptive transfer of b3a2-CTLs. One representative plot of four untreated and five b3a2-CTL–treated HLA-A2tg CML mice is shown. (C and F) LSC numbers per mouse 1 d after adoptive transfer. (D and G) Equal numbers of lin⁻ cells were plated in methylcellulose and BCR/ABL-GFP⁺ colonies were enumerated 7 d later by fluorescence microscopy. (E and H) 3 × 10⁶ BM cells from HLA-A2tg CML mice left untreated (n = 4–8), treated with BCR/ABL b3a2-junction peptide-specific HLA-A2tg CTLs (n = 4), or treated with HIV SL9 peptide-specific HLA-A2tg CD8⁺ T cells (+SL9-CTLs, n = 6) were secondarily transplanted into irradiated (6.5 Gy) HLA-A2tg mice. Kaplan-Meier survival curves resulting from secondary transplantations are shown. Data are displayed as mean ± SEM. Statistics: Student’s t test (C, D, F, and G) and log-rank test (E and H). *, P < 0.05; **, P < 0.01.