Long-lasting decrease of CD4⁺/CD45RA⁺T cells in HCL patients after 2-chlorodeoxyadenosine (2-CdA) treatment

Abstract

The CD45RA and CD45RO isoforms of the leukocyte common antigen identify functionally distinct CD4⁺ T cell subsets: CD4⁺/CD45RA⁺cells which represent a more ‘naive’ stage of T cell compartment and CD4⁺/CD45RO⁺ ‘memory’ cells. Phenotypic and functional abnormalities in T cell compartment have been frequently reported in patients with hairy cell leukemia (HCL) and, in more recent studies, a significant reduction in the absolute number of CD4⁺ lymphocytes bearing the CD45RO antigen has also been recorded. In our study we evaluated the CD45RA and CD45RO expression on CD4⁺ T cells by three-color staining in flow cytometry in 38 HCL patients, 19 untreated and 19 previously treated with 2-chlorodeoxyadenosine (2-CdA), administered at a daily dose of 0.1 mg/kg c.i. for 7 days. In HCL untreated patients, the proportion and the absolute number of CD4⁺/CD45RA⁺ and of CD4⁺/CD45RO⁺ T cell subsets were similar to normal controls. In contrast, HCL patients at 3–5 years by the end of treatment with 2-CdA, together with a reduction in the absolute number of CD4⁺ T cells, showed a persistent and significant decrease in the proportion and absolute number of CD4⁺/CD45RA⁺ cells as compared with both untreated HCL patients and normal controls (41 ± 16% vs 57 ± 14% and vs 65 ± 7%) (P = 0.01 and 0.0001) and (0.201 ± 0.137 × 10⁹/l vs0.549 ± 0.238 × 10⁹/l and vs0.696 ± 0.078 × 10⁹/l) (P = 0.00009 and P = 0.00001). In addition, together with the reduction of CD4⁺/CD45RA⁺ cells, we recorded a concomitant increase in the proportion of the CD4⁺/CD45RO⁺cells as compared to untreated HCL patients and normal controls (62 ± 16% vs 47 ± 15% and vs 42 ± 12%) (P = 0.08 and 0.02). These findings may suggest that CD4⁺/CD45RA⁺ cells are more sensitive than CD4⁺/CD45RO⁺ to the toxic effect of 2-CdA.