Protective Immunity Transferred by Infusion of Cytomegalovirus-Specific CD8+ T Cells within Donor Grafts: Its Associations with Cytomegalovirus Reactivation.

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Presentation transcript:

Protective Immunity Transferred by Infusion of Cytomegalovirus-Specific CD8+ T Cells within Donor Grafts: Its Associations with Cytomegalovirus Reactivation Following Unmanipulated Allogeneic Hematopoietic Stem Cell Transplantation Xiao-Hua Luo, Xiao-Jun Huang, Kai-Yan Liu, Lan-Ping Xu, Dai-Hong Liu Biology of Blood and Marrow Transplantation Volume 16, Issue 7, Pages 994-1004 (July 2010) DOI: 10.1016/j.bbmt.2010.02.007 Copyright © 2010 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 Relationship between TEMRA and TEM in allografts and CMV reactivation after HSCT. (A) The absolute numbers of TEMRA in allografts were significantly higher in patients with CMV reactivation in the presence of sufficient infusion of TEM (≥0.208 × 106/kg). (B) The absolute numbers of TEM in allografs were not significantly different in patients with CMV reactivation and those without CMV reactivation, regardless of the TEM content infused. Only significant P values are shown. “High” and “low” were introduced as above and below the median value, respectively (TEMRA, 0.177 × 106/kg; TEM, 0.208 × 106/kg). Biology of Blood and Marrow Transplantation 2010 16, 994-1004DOI: (10.1016/j.bbmt.2010.02.007) Copyright © 2010 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 Expansion of CTLCMV TCM cells on CMV reactivation post-HSCT. Using flow-based frequency enumeration and absolute lymphocyte counts, absolute numbers of CTLCMV cells and subsets were calculated for healthy donors (n = 17) and HSCT recipients (n = 44) at regular intervals on days +30, +60, and +90. (A) The CTLCMV with TCM phenotype was significantly higher at days +30 and +60 post-HSCT in patients with CMV reactivation compared with patients without CMV reactivation. (B and C) The absolute counts of CD8+ T cells and CTLCMV were not statistically significantly different between the 2 groups. Bars indicate median values. Only significant P values are shown. Biology of Blood and Marrow Transplantation 2010 16, 994-1004DOI: (10.1016/j.bbmt.2010.02.007) Copyright © 2010 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 3 Relationship between number of CTLCMV TEMRA cells transplanted and the recovery kinetics of circulating CTLCMV subsets after HSCT. Bars indicate median values. The frequencies of circulating CTLCMV TNaive, CTLCMV TCM, and CTLCMV TCM at day +90 and CTLCMV TEMRA at day +60 post-HSCT were higher in HSCT recipients with more CTLCMV TEMRA infused. Only significant P values are shown. “High TEMRA infusion” and “low TEMRA infusion” was introduced as above or below the median value of TEMRA cells in allografts (ie, 0.177 × 106/kg). Biology of Blood and Marrow Transplantation 2010 16, 994-1004DOI: (10.1016/j.bbmt.2010.02.007) Copyright © 2010 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 4 (A and B) Sources of CTLCMV responses in peripheral blood in relation to CMV infection as measured by CMV-DNA copies. The number of days after HSCT is shown on the x-axis. CTLCMV (HLA-A∗0201+ CD8+ T cells [patient origin; black] and HLA-A∗2402+ CD8+ T cells [donor origin; red]) are expressed as percentage of circulating CD8+ T cells (left, y-axis). CMV reactivation is expressed as CMV-DNA copies in peripheral blood (right, y-axis, green). (C-F) Relative proportions of CTLCMV cells in 4 distinct maturation stages (from least mature to more mature: TNaive, TCM, TEM, TEMRA) assessed by flow cytometry. The majority of CTLCMV cells were from donors early post-HSCT, and subsets of CTLCMV differed between donors and patients. Biology of Blood and Marrow Transplantation 2010 16, 994-1004DOI: (10.1016/j.bbmt.2010.02.007) Copyright © 2010 American Society for Blood and Marrow Transplantation Terms and Conditions