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Clin Immunol. 2012 Oct;145(1):19-26. doi: 10.1016/j.clim.2012.07.007. Epub 2012 Jul 21.

Peripheral accumulation of newly produced T and B lymphocytes in natalizumab-treated multiple sclerosis patients.

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  • 1Biotechnology Laboratory, Diagnostics Department, Spedali Civili di Brescia, P.le Spedali Civili 1, 25123 Brescia, Italy. zanotti.cinzia@gmail.com

Abstract

The anti-α4 monoclonal antibody natalizumab inhibits lymphocyte extravasation into the central nervous system and increases peripheral T and B lymphocytes in multiple sclerosis patients. To investigate whether the lymphocyte accumulation was due to a higher lymphocyte production, an altered homeostasis, or a differential transmigration of lymphocyte subsets through endothelia, T-cell receptor excision circles and kappa-deleting recombination excision circles were quantified before and after treatment, T-cell receptor repertoire was analyzed by spectratyping, and T- and B-lymphocyte subset migration was studied using transwell coated with vascular and lymphatic endothelial cells. We found that the number of newly produced T and B lymphocytes is increased because of a high release and of a low propensity of naïve subsets to migrate across endothelial cells. In some patients this resulted in an enlargement of T-cell heterogeneity. Because new lymphocyte production ensures the integrity of immune surveillance, its quantification could be used to monitor natalizumab therapy safety.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID:
22892399
[PubMed - indexed for MEDLINE]
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