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

During immunosuppression, cytomegalovirus (CMV) can reactivate and cause se rious clinical problems. Normally, abundant virus replication is suppressed by immune effector mechanisms. To study the interaction between CD8(+) T c ells and persisting viruses, frequencies and phenotypes of CMV-specific CD8 (+) T cells were determined in healthy individuals and compared to those in renal transplant recipients. In healthy donors, function of circulating vi rus-specific CD8(+) T cells, as measured by peptide-induced interferon gamm a (IFN-gamma) production, but not the number of virus-specific T cells enum erated by binding of specific tetrameric peptide/HLA complexes, correlated with the number of CMV-specific IFN-gamma -secreting CD4(+) helper T cells. Circulating CMV-specific CD8(+) T cells did not express CCR7 and may there fore not be able to recirculate through peripheral lymph nodes. Based on co expression of CD27 and CD45R0 most CMV-specific T cells in healthy donors a ppeared to be memory-type cells. Remarkably, frequencies of CMV-specific CD 8(+) 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, CD45R0(+)CD27(-)CCR7(-) or CD45RA(+)CD27(-) CCR7(-) and contained both granzyme B and perforin. Our data show that In r esponse to immunosuppressive medication quantitative and qualitative change s occur In the CD8(+) T-cell compartment. These adaptations may be Instrume ntal to maintain CMV latency. (C) 2001 by The American Society of Hematolog y.