Newly produced T and B lymphocytes and T-cell receptor repertoire diversity are reduced in peripheral blood of fingolimod-treated multiple sclerosis patients.
BACKGROUND
Fingolimod inhibits lymphocyte egress from lymphoid tissues, thus altering the composition of the peripheral lymphocyte pool of multiple sclerosis patients.


OBJECTIVE
The objective of this paper is to evaluate whether fingolimod determines a decrease of newly produced T- and B-lymphocytes in the blood and a reduction in the T-cell receptor repertoire diversity that may affect immune surveillance.


METHODS
Blood samples were obtained from multiple sclerosis patients before fingolimod therapy initiation and then after six and 12 months. Newly produced T and B lymphocytes were measured by quantifying T-cell receptor excision circles and K-deleting recombination excision circles by real-time PCR, while recent thymic emigrants, naive CD8(+) lymphocytes, immature and naive B cells were determined by immune phenotyping. T-cell receptor repertoire was analyzed by complementarity determining region 3 spectratyping.


RESULTS
Newly produced T and B lymphocytes were significantly reduced in peripheral blood of fingolimod-treated patients. The decrease was particularly evident in the T-cell compartment. T-cell repertoire restrictions, already present before therapy, significantly increased after 12 months of treatment.


CONCLUSIONS
These results do not have direct clinical implications but they may be useful for further understanding the mode of action of this immunotherapy for multiple sclerosis patients.
CREA, Diagnostics Department.
M
M
Chiarini
CREA, Diagnostics Department.
A
A
Sottini
CREA, Diagnostics Department.
D
D
Bertoli
CREA, Diagnostics Department.
F
F
Serana
CREA, Diagnostics Department.
L
L
Caimi
Multiple Sclerosis Center, Spedali Civili of Brescia, Italy.
S
S
Rasia
Multiple Sclerosis Center, Spedali Civili of Brescia, Italy.
R
R
Capra
CREA, Diagnostics Department limberti@yahoo.it.
L
L
Imberti
D000328:Adult; D001402:B-Lymphocytes / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000188:drug therapy*; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects*; D016176:T-Lymphocyte Subsets / Q000187:drug effects*
D007166:Immunosuppressive Agents; D011948:Receptors, Antigen, T-Cell; D000068876:Fingolimod Hydrochloride
B-lymphocyte subsets; KRECs; Multiple sclerosis; T-cell receptor repertoire; T-lymphocyte subsets; TRECs; fingolimod; immunological monitoring