Renewal of the T-cell compartment in multiple sclerosis patients treated with glatiramer acetate.
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.
Chiarini
M
M
Laboratorio di Biotecnologie, Diagnostics Department, Spedali Civili di Brescia, Italy.
Sottini
A
A
Ghidini
C
C
Zanotti
C
C
Serana
F
F
Rottoli
M
M
Zaffaroni
M
M
Bergamaschi
R
R
Cordioli
C
C
Capra
R
R
Imberti
L
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005434:Flow Cytometry; D000068717:Glatiramer Acetate; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007156:Immunologic Memory / Q000187:drug effects; D016130:Immunophenotyping / Q000379:methods; D038041:Lymphopoiesis / Q000187:drug effects*; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology; D010455:Peptides / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D007155:Immunologic Factors; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D000068717:Glatiramer Acetate