Blood, Vol. 94 No. 8 (October 15), 1999:
pp. 2790-2799
Analysis of T Cells in Paroxysmal Nocturnal Hemoglobinuria Provides
Direct Evidence That Thymic T-Cell Production Declines With Age
Stephen J. Richards,
Gareth J. Morgan, and
Peter Hillmen
From the Haematological Malignancy Diagnostic Service, Leeds General
Infirmary, Leeds, UK.
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
(CD45RACD45R0+) 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.
