Abstract
Naive T cells are migratory cells that continuously recirculate between blood and lymphoid tissues. Antigen-specific stimulation of T cells within the lymph nodes reprograms the trafficking properties of T cells by inducing a specific set of adhesion molecules and chemokine receptors on their surface which allow these activated and effector T cells to effectively and specifically home to extralymphoid organs. The observations of organ-specific homing of T cells initiated the development of therapeutic strategies targeting adhesion receptors for organ-specific inhibition of chronic inflammation. As most adhesion receptors have additional immune functions besides mediating leukocyte trafficking, these drugs may have additional immunomodulatory effects. Therapeutic targeting of T-cell trafficking to the central nervous system is the underlying concept of a novel treatment of relapsing remitting multiple sclerosis with the humanized anti-α-4-integrin antibody natalizumab. In this chapter, we describe a possible preclinical in vivo approach to directly visualize the therapeutic efficacy of a given drug in inhibiting T-cell homing to a certain organ at the example of the potential of natalizumab to inhibit the trafficking of human T cells to the inflamed central nervous system in an animal model of multiple sclerosis.
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Acknowledgments
We owe special thanks to Heidi Tardent for excellent microsurgical preparations and to Lucienne Tritten for critical comments on this chapter. This work has been supported by the National Multiple Sclerosis Society (NMSS, USA), the Swiss MS Society, and the Bern University Research Foundation. We thank Susan (Goelz): (BiogenIdec, USA) for the gift of Natalizumab. CC has been funded by the Fondation pour la Recherche Médicale (FRM, France), the Association pour la Recherche sur la Sclérose En Plaques (ARSEP, France), and the NMSS.
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Coisne, C., Engelhardt, B. (2010). Preclinical Testing of Strategies for Therapeutic Targeting of Human T-Cell Trafficking In Vivo. In: Marelli-Berg, F., Nourshargh, S. (eds) T-Cell Trafficking. Methods in Molecular Biology, vol 616. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-461-6_17
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DOI: https://doi.org/10.1007/978-1-60761-461-6_17
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