Chronic myelogenous leukemia shapes host immunity by selective deletion of high-avidity leukemia-specific T cells
J. Clin. Invest. Jeffrey J. Molldrem, et al. 111:639 doi:10.1172/JCI16398 [Go to this article.]

Figure 6
High-avidity PR1-CTLs undergo apoptosis 18 hours after coincubation with HLA-A2⁺ CML cells that overexpress proteinase 3. High- and low-avidity PR1-CTLs were combined in a 1:1 ratio, based upon the number of tetramer-positive cells, with CML BM cells from untreated HLA-A2⁺ and HLA-A2^– patients. Annexin V staining was measured on live cells, based on PI staining, 18 hours after coincubation. The percentage of CD8⁺ cells that are tetramer-positive is shown in the left panels, and the percentage of tetramer-positive cells that stain with annexin V are shown in the remaining panels. (a) Annexin V was upregulated in the high-avidity PR1-CTLs after coincubation with HLA-A2⁺ cells, but not after coincubation with HLA-A2^– cells. Remaining low-avidity PR1-CTLs in the culture did not upregulate annexin V. (b) In contrast, low-avidity PR1-CTLs did not upregulate annexin V after coincubation with either HLA-A2⁺ or HLA-A2^– CML BM cells. (c) Overall MHC-I expression and proteinase 3 expression was similar in both CML BM target cells, as measured by surface staining with pan-HLA-A,B,C Ab. (d) Proteinase 3 expression was 2.8- and 3.3-fold higher in the HLA-A2⁺ and the HLA-A2^– patient BM, respectively, compared with healthy donor BM cells.