TIME-COURSE ANALYSIS OF CD25 AND HLA-DR EXPRESSION ON LYMPHOCYTES IN INTERFERON-BETA 1B-TREATED MULTIPLE-SCLEROSIS PATIENTS

To identify immunological markers that could be used to monitor relaps ing-remitting multiple sclerosis (RRMS) course/activity during interfe ron beta 1b (IFN beta 1b) therapy we longitudinally studied HLA-DR and CD25 expression by T lymphocytes in 15 IFN beta 1b-treated RRMS patie nts. Peripheral blood T cell subsets were analysed before therapy (T0) , and after 1 (T1), 2 (T2), 3 (T3), 6 (T4) and 12 (T5) months after th erapy initiation. HLA-DR expression and the CD3+HLA-DR+ T cell number showed a peculiar trend in almost all(14/15) the patients: a significa nt decrease at T1 and T2 followed by a return to pre-treatment levels from T3 to T5. At T1 and T2, eight patients showed on up-regulation of CD25 on CD4, as well as an increase in the CD4+CD25+ cell number. How ever, a marked, significant reduction of this T cell subset was observ ed in all the patients at T3, followed by the Progressive return to pr e-treatment values from T4 to T5. All the patients developed anti-IFN beta 1b 'binding' antibodies within the first three months of therapy. Our findings demonstrate that (1) the expression of HLA-DR and CD25 o n T cells, as well as the number of circulating CD3+HLA-DR+ and CD4+CD 25+ cells, ore only transiently reduced in vivo in IFN beta 1b-treated RRMS patients, (2) the expression of HLA-DR and CD25 on T lymphocytes cannot be used to monitor MS course/activity during IFN beta 1b thera py (3) the long-lasting beneficial effect of IFN beta 1b on RRMS repor ted in the literature cannot be explained by the down-regulation of MH C class II antigens and/or interleukin-2 receptor expression induced b y this cytokine.