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

M. Chiarini, A. Sottini, C. Ghidini, C. Zanotti, F. Serana, M. Rottoli, M. Zaffaroni, R. Bergamaschi, C. Cordioli, R. Capra, L. Imberti

Research output: Contribution to journalArticle

Abstract

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 thymicnaive 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 thymicnaive 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.

Original languageEnglish
Pages (from-to)218-227
Number of pages10
JournalMultiple Sclerosis Journal
Volume16
Issue number2
DOIs
Publication statusPublished - Feb 2010

Fingerprint

Multiple Sclerosis
T-Lymphocytes
Helper-Inducer T-Lymphocytes
Glatiramer Acetate
T-Cell Antigen Receptor
Tissue Donors

Keywords

  • Disease modifying therapies
  • Glatiramer acetate
  • Immunologic monitoring
  • Immunology
  • Multiple sclerosis
  • T-cell receptor
  • T-cells
  • Thymicnaive T helper cells

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Chiarini, M., Sottini, A., Ghidini, C., Zanotti, C., Serana, F., Rottoli, M., ... Imberti, L. (2010). Renewal of the T-cell compartment in multiple sclerosis patients treated with glatiramer acetate. Multiple Sclerosis Journal, 16(2), 218-227. https://doi.org/10.1177/1352458509355460

Renewal of the T-cell compartment in multiple sclerosis patients treated with glatiramer acetate. / Chiarini, M.; Sottini, A.; Ghidini, C.; Zanotti, C.; Serana, F.; Rottoli, M.; Zaffaroni, M.; Bergamaschi, R.; Cordioli, C.; Capra, R.; Imberti, L.

In: Multiple Sclerosis Journal, Vol. 16, No. 2, 02.2010, p. 218-227.

Research output: Contribution to journalArticle

Chiarini, M, Sottini, A, Ghidini, C, Zanotti, C, Serana, F, Rottoli, M, Zaffaroni, M, Bergamaschi, R, Cordioli, C, Capra, R & Imberti, L 2010, 'Renewal of the T-cell compartment in multiple sclerosis patients treated with glatiramer acetate', Multiple Sclerosis Journal, vol. 16, no. 2, pp. 218-227. https://doi.org/10.1177/1352458509355460
Chiarini, M. ; Sottini, A. ; Ghidini, C. ; Zanotti, C. ; Serana, F. ; Rottoli, M. ; Zaffaroni, M. ; Bergamaschi, R. ; Cordioli, C. ; Capra, R. ; Imberti, L. / Renewal of the T-cell compartment in multiple sclerosis patients treated with glatiramer acetate. In: Multiple Sclerosis Journal. 2010 ; Vol. 16, No. 2. pp. 218-227.
@article{643546444472436f90581a1b164066d9,
title = "Renewal of the T-cell compartment in multiple sclerosis patients treated with glatiramer acetate",
abstract = "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 thymicnaive 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 thymicnaive 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.",
keywords = "Disease modifying therapies, Glatiramer acetate, Immunologic monitoring, Immunology, Multiple sclerosis, T-cell receptor, T-cells, Thymicnaive T helper cells",
author = "M. Chiarini and A. Sottini and C. Ghidini and C. Zanotti and F. Serana and M. Rottoli and M. Zaffaroni and R. Bergamaschi and C. Cordioli and R. Capra and L. Imberti",
year = "2010",
month = "2",
doi = "10.1177/1352458509355460",
language = "English",
volume = "16",
pages = "218--227",
journal = "Multiple Sclerosis",
issn = "1352-4585",
publisher = "SAGE Publications Ltd",
number = "2",

}

TY - JOUR

T1 - Renewal of the T-cell compartment in multiple sclerosis patients treated with glatiramer acetate

AU - Chiarini, M.

AU - Sottini, A.

AU - Ghidini, C.

AU - Zanotti, C.

AU - Serana, F.

AU - Rottoli, M.

AU - Zaffaroni, M.

AU - Bergamaschi, R.

AU - Cordioli, C.

AU - Capra, R.

AU - Imberti, L.

PY - 2010/2

Y1 - 2010/2

N2 - 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 thymicnaive 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 thymicnaive 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.

AB - 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 thymicnaive 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 thymicnaive 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.

KW - Disease modifying therapies

KW - Glatiramer acetate

KW - Immunologic monitoring

KW - Immunology

KW - Multiple sclerosis

KW - T-cell receptor

KW - T-cells

KW - Thymicnaive T helper cells

UR - http://www.scopus.com/inward/record.url?scp=76449085393&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=76449085393&partnerID=8YFLogxK

U2 - 10.1177/1352458509355460

DO - 10.1177/1352458509355460

M3 - Article

C2 - 20007428

AN - SCOPUS:76449085393

VL - 16

SP - 218

EP - 227

JO - Multiple Sclerosis

JF - Multiple Sclerosis

SN - 1352-4585

IS - 2

ER -