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

Relationship between T_EMRA and T_EM in allografts and CMV reactivation after HSCT. (A) The absolute numbers of T_EMRA in allografts were significantly higher in patients with CMV reactivation in the presence of sufficient infusion of T_EM (≥0.208 × 10⁶/kg). (B) The absolute numbers of T_EM in allografs were not significantly different in patients with CMV reactivation and those without CMV reactivation, regardless of the T_EM content infused. Only significant P values are shown. “High” and “low” were introduced as above and below the median value, respectively (T_EMRA, 0.177 × 10⁶/kg; T_EM, 0.208 × 10⁶/kg).

Expansion of CTL_CMV T_CM cells on CMV reactivation post-HSCT. Using flow-based frequency enumeration and absolute lymphocyte counts, absolute numbers of CTL_CMV 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 CTL_CMV with T_CM 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 CTL_CMV were not statistically significantly different between the 2 groups. Bars indicate median values. Only significant P values are shown.

Relationship between number of CTL_CMV T_EMRA cells transplanted and the recovery kinetics of circulating CTL_CMV subsets after HSCT. Bars indicate median values. The frequencies of circulating CTL_CMV T_Naive, CTL_CMV T_CM, and CTL_CMV T_CM at day +90 and CTL_CMV T_EMRA at day +60 post-HSCT were higher in HSCT recipients with more CTL_CMV T_EMRA infused. Only significant P values are shown. “High T_EMRA infusion” and “low T_EMRA infusion” was introduced as above or below the median value of T_EMRA cells in allografts (ie, 0.177 × 10⁶/kg).

(A and B) Sources of CTL_CMV 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. CTL_CMV (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 CTL_CMV cells in 4 distinct maturation stages (from least mature to more mature: T_Naive, T_CM, T_EM, T_EMRA) assessed by flow cytometry. The majority of CTL_CMV cells were from donors early post-HSCT, and subsets of CTL_CMV differed between donors and patients.