Rapid reconstitution of CMV-specific T-cells after stem-cell transplantation.

Abstract

As reconstitution of virus-specific T-cells is critical to control cytomegalovirus (CMV)-viremia following stem-cell transplantation (SCT), we characterized the dynamics in CMV-specific T-cell reconstitution after SCT. Cytomegalovirus-specific T-cells from 51 SCT-recipients were prospectively quantified and phenotypically characterised by intracellular cytokine-staining after specific stimulation and HLA class-I-specific pentamers using flow cytometry. Cytomegalovirus-specific CD4 T-cells reconstituted after a median of 2.3 (IQR, 2.0-3.0)weeks following autografting, and 4.0 (IQR, 3.0-5.6)weeks after allografting, with CMV-specific T-cells originating from donors and/or recipients. The time for reconstitution of CMV-specific CD4 and CD8 T-cells did not differ (P=.58). Factors delaying the time to initial reconstitution of CMV-specific CD4 T-cells included a negative recipient serostatus (P=.016) and CMV-viremia (P=.026). Percentages of CMV-specific CD4 T-cells significantly increased over time and reached a plateau after 90days (P=.043). Relative CMV-specific CD4 T-cell levels remained higher in long-term transplant recipients compared with those in controls (P<.0001). However, due to persisting lymphopenia, absolute numbers of CMV-specific T-cells were similar as in controls. Cytomegalovirus-specific T-cells rapidly reconstitute after SCT and their percentages remain high in the long term. In the face of persistent lymphopenia, this results in similar absolute numbers of CMV-specific T-cells as in controls to ensure sufficient pathogen control.