Analysis of T cells in paroxysmal nocturnal hemoglobinuria provides direct evidence that thymic T-cell production declines with age.
Peripheral blood T cells in patients with paroxysmal nocturnal hemoglobinuria (PNH) comprise a mixture of residual normal and glycosylphosphatidylinositol (GPI)-deficient PNH cells. Using multicolor flow cytometry, we demonstrated significant differences between the proportions of naive and memory cells within these populations. PNH T cells comprise mainly naive cells (CD45RA(+)CD45R0(-)), whereas normal T cells in the same patients were predominantly memory (CD45RA(-)CD45R0(+)) cells. Functional analyses showed that GPI-deficient CD45RA(+) T cells can convert to a CD45R0(+) phenotype. We present data from a PNH patient in remission for 20 years who still had significant numbers of GPI-deficient T cells; these showed a normal distribution of naive and memory components. The predominantly naive phenotype of GPI-deficient T cells seen in PNH patients with active disease likely reflects the phenotype of recent normal thymic emigrants. In patients where hematopoiesis was predominantly derived from the PNH stem cell, absolute numbers of both naive PNH CD4(+) cells and CD8(+) cells show an inverse correlation with patient age, implying this age-related decline in T-cell production is secondary to a decrease in thymic activity rather than a stem cell defect.
Richards
S J
SJ
Haematological Malignancy Diagnostic Service, Leeds General Infirmary, Leeds, UK.
Morgan
G J
GJ
Hillmen
P
P
D000328:Adult; D000368:Aged; D000375:Aging / Q000276:immunology*; D015703:Antigens, CD / Q000032:analysis; D000071178:CD48 Antigen; D004906:Erythrocyte Count; D005260:Female; D017261:Glycosylphosphatidylinositols / Q000172:deficiency / Q000235:genetics; D006684:HLA-DR Antigens / Q000032:analysis; D006457:Hemoglobinuria, Paroxysmal / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000032:analysis; D007958:Leukocyte Count; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets
D015703:Antigens, CD; D000071178:CD48 Antigen; D017261:Glycosylphosphatidylinositols; D006684:HLA-DR Antigens; D017493:Leukocyte Common Antigens