Differentiation of cytomegalovirus-specific CD8(+) T cells in healthy and immunosuppressed virus carriers

During immunosuppression, cytomegalovirus (CMV) can reactivate and cause serious clinical problems. Normally, abundant virus replication is suppressed by immune effector mechanisms. To study the interaction between CD81 T cells and persisting viruses, frequencies and phenotypes of CMVspecific CD81 T cells were determined in healthy individuals and compared to those in renal transplant recipients. In healthy donors, function of circulating virus-specific CD81 T cells, as measured by peptideinduced interferon g (IFN-g) production, but not the number of virus-specific T cells enumerated by binding of specific tetrameric peptide/HLA complexes, correlated with the number of CMV-specific IFN-g‐secreting CD41 helper T cells. Circulating CMVspecific CD81 T cells did not express CCR7 and may therefore not be able to recirculate through peripheral lymph nodes. Based on coexpression of CD27 and CD45R0 most CMV-specific T cells in healthy donors appeared to be memory-type cells. Remarkably, frequencies of CMV-specific CD81 T cells were significantly higher in immunosuppressed individuals than in healthy donors. In these patients CMV-specific cells predominantly had an effector phenotype, that is, CD45R01CD272CCR72 or CD45RA1CD272CCR72 and contained both granzyme B and perforin. Our data show that in response to immunosuppressive medication quantitative and qualitative changes occur in the CD81 T-cell compartment. These adaptations may be instrumental to maintain CMV latency. (Blood. 2001;98:754-761)