Monitoring of cytomegalovirus-specific CD8+ T-cell response with major histocompatibility complex pentamers in kidney transplant recipients

Introduction

Cytomegalovirus (CMV) can reactivate causing serious clinical problems during immunosuppression. CMV-specific CD8⁺ T cells play an important role in the control of CMV reactivation. Using pentameric major histocompatibility complex (MHC) peptide complexes, we investigated cellular immune responses to CMV among healthy individuals and kidney transplantation recipients in Korea, which is an endemic area of CMV infection.

Materials and methods

Analysis of CMV-specific T cells was performed on 28 healthy individuals and 40 recipients who bore human leukocyte antigen (HLA)-A2 or -A24. CMV pp65 pentamer-binding cells incubated with various monoclonal antibodies were measured by four-color flow cytometry.

Results

Detectable levels of pentamer⁺ CD8⁺ T cells were present in 109/139 samples (78.4%) that stained with the A*02NLV-pentamer, while 15/67 samples (22.4%) stained with the A*24QYD-pentamer (P < .01). Among patients with HLA-A2, 22/24 (91.7%) samples showing positive CMV antigenemia revealed detectable pentamer⁺ CD8⁺ T cells, while 87/115 (75.7%) displaying negative CMV antigenemia had detectable pentamer⁺ CD8⁺ T cells (P = .04). There was no significant difference in percentages of pentamer⁺ CD8⁺ T cells between patients who did versus who did not experience episodes of CMV infection. The subpopulation of CMV-specific CD8⁺ T cells in transplantation recipients was evaluated using phenotypic markers; memory cells comprised the majority of the CMV-specific CD8⁺ T-cell population.

Conclusion

The A*02NLV-pentamer complex was useful to monitor CMV-specific T cells. However, MHC pentamer-based techniques did not provide a clear distinction between patients who are or are not at risk for CMV infection.