Analysis of T cells in paroxysmal nocturnal hemoglobinuria provides directevidence that thymic T-cell production declines with age

Peripheral blood T cells in patients with paroxysmal nocturnal hemoglobinur ia (PNH) comprise a mixture of residual normal and glycosylphosphatidylinos itol (GPI)-deficient PNH cells. Using multicolor flow cytometry we demonstr ated significant differences between the proportions of naive and memory ce lls within these populations. PNH T cells comprise mainly naive cells (CD45 RA(+)CD45R0(-)), whereas normal T cells in the same patients were predomina ntly memory (CD45RA(-)CD45R0(+)) cells. Functional analyses showed that GPI -deficient CD45RA(+) T cells can convert to a CD45R0(+) phenotype. We prese nt data from a PNH patient in remission for 20 years who still had signific ant numbers of GPI-deficient T cells; these showed a normal distribution of naive and memory components. The predominantly naive phenotype of GPI-defi cient T cells seen in PNH patients with active disease likely reflects the phenotype of recent normal thymic emigrants. In patients where hematopoiesi s was predominantly derived from the PNH stem cell, absolute numbers of bot h naive PNH CD4(+) cells and CD8(+) cells show an inverse correlation with patient age, implying this age-related decline in T-cell production is seco ndary to a decrease in thymic activity rather than a stem cell defect. (C) 1999 by The American Society of Hematology.