CD25 Blockade Delays Regulatory T Cell Reconstitution and Does Not Prevent Graft- versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation

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Presentation transcript:

CD25 Blockade Delays Regulatory T Cell Reconstitution and Does Not Prevent Graft- versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation Frederick L. Locke, Joseph Pidala, Barry Storer, Paul J. Martin, Michael A. Pulsipher, Thomas R. Chauncey, Niels Jacobsen, Nicolaus Kröger, Irwin Walker, Susan Light, Bronwen E. Shaw, Francisca Beato, Ginna G. Laport, Auayporn Nademanee, Armand Keating, Gerard Socie, Claudio Anasetti Biology of Blood and Marrow Transplantation Volume 23, Issue 3, Pages 405-411 (March 2017) DOI: 10.1016/j.bbmt.2016.12.624 Copyright © 2017 Terms and Conditions

Figure 1 Cumulative incidence of grade III-IV acute GVHD (A) and chronic GVHD (B) according to treatment with placebo (arm A), daclizumab 0.3 mg/kg (arm B), or daclizumab 1.2 mg/kg (arm C). Biology of Blood and Marrow Transplantation 2017 23, 405-411DOI: (10.1016/j.bbmt.2016.12.624) Copyright © 2017 Terms and Conditions

Figure 2 Cumulative incidence curves for nonrelapse mortality (A) and relapse (B), and Kaplan-Meier curve for overall survival (C), according to treatment with placebo, daclizumab 0.3 mg/kg, or daclizumab 1.2 mg/kg. Biology of Blood and Marrow Transplantation 2017 23, 405-411DOI: (10.1016/j.bbmt.2016.12.624) Copyright © 2017 Terms and Conditions

Figure 3 Flow cytometry analysis of lymphocyte subsets according to study arm. (A) Administration of daclizumab decreased the percentage of T cells expressing CD25 as measured by 7G7, a non–daclizumab-competing antibody against CD25, at days +11 to +35 and days +36 to +80, but not at days +81 to +101. (B) Daclizumab administration decreased the percentage of T cells with free CD25-binding sites at days +11 to +35 and days +36 to +80. (C) Daclizumab was effectively bound to CD25+ T cells in vivo at days +11 to +35, days +36 to +90, and days +81 to +101. (D) The percentage of Tregs in the CD4 T cell population (CD3+CD4+CD127lowCD25+FOXP3+) was decreased at days +11 to +35 and days +81 to +101. (E) The percentage of CD4 cells with a central memory phenotype (CD3+CD4+CCR7+CD45RA-) was increased at 1 year (LTFU). (F) The percentage of CD8 cells with a central memory phenotype (CD3+CD8+CCR7+CD45RA-) was increased at days +81 to +101. *P < .0001, 2-sample t-test. In all graphs, the box extends the interquartile range (IQR) from the 25th to 75th percentiles, the whiskers extend to the nearest data point 1.5 times the IQR beyond the 25th and 75th percentiles, and the dots represent data >1.5 times the IQR above the 75th quartile or below the 25th quartile. In some cases (C), the box and whiskers are all at 0 and not represented on the graph. Biology of Blood and Marrow Transplantation 2017 23, 405-411DOI: (10.1016/j.bbmt.2016.12.624) Copyright © 2017 Terms and Conditions