Renewal of the T-cell compartment in multiple sclerosis patients treated with glatiramer acetate

作者：Chiarini M; Sottini A; Ghidini C; Zanotti C; Serana F; Rottoli M; Zaffaroni M; Bergamaschi R; Cordioli C; Capra R; Imberti L^*

来源：Multiple Sclerosis, 2010, 16(2): 218-227.

DOI：10.1177/1352458509355460

• disease modifying therapies
• glatiramer acetate
• immunologic monitoring
• immunology
• multiple sclerosis
• (thymic)naive T helper cells
• T-cell receptor
• T-cells

The immunomodulating activity of glatiramer acetate on T-cells of multiple sclerosis patients has only been partially clarified. The objective of this work was to investigate whether glatiramer acetate modifies thymic release of newly produced T-cells and the peripheral composition of the T-cell repertoire. T-cell receptor excision circles, (thymic)naive (CD4(+)CD45RA(+)CCR7(+)CD31(+)) T helper cells, and central (CD4(+)CD45RA(-)CCR7(+)) and effector (CD4(+)CD45RA(-)CCR7(-)) memory T-cells were evaluated in 89 untreated patients, 84 patients treated for at least 1 year, and 31 patients beginning treatment at the time of inclusion in the study and then followed-up for 12 months; controls were 81 healthy donors. The T-cell repertoire was analysed in selected samples. The percentage of (thymic)naive T helper cells was diminished in untreated patients, but rose to control values in treated subjects; a decrease in central memory T-cells was also observed in treated patients. Follow-up patients could be divided into two subgroups, one showing unmodified (thymic)naive T helper cells and T-cell diversity, the other in which the increased release of new T-cells was accompanied by modifications of the T-cell repertoire. Glatiramer acetate modifies the peripheral T-cell pool by activating a thymopoietic pathway of T-cell release that leads to a different setting of T-cell diversity and, likely, to a dilution of autoreactive T-cells.

• 出版日期2010-2