Trans-Endothelial Migration of Memory T Cells Is Impaired in Alemtuzumab-Treated Multiple Sclerosis Patients

Kristy Nguyen; Pierre Juillard; Simon Hawke; Georges E Grau; Felix Marsh-Wakefield

doi:10.3390/jcm11216266

Trans-Endothelial Migration of Memory T Cells Is Impaired in Alemtuzumab-Treated Multiple Sclerosis Patients

J Clin Med. 2022 Oct 24;11(21):6266. doi: 10.3390/jcm11216266.

Authors

Kristy Nguyen¹, Pierre Juillard¹, Simon Hawke^{1

2}, Georges E Grau¹, Felix Marsh-Wakefield^{1

3

4}

Affiliations

¹ Vascular Immunology Unit, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
² Central West Neurology and Neurosurgery, Orange, NSW 2800, Australia.
³ Liver Injury and Cancer Program, Centenary Institute, Sydney, NSW 2050, Australia.
⁴ Human Cancer and Viral Immunology Laboratory, The University of Sydney, Sydney, NSW 2006, Australia.

Abstract

The breakdown of the blood-brain barrier (BBB) and the trans-endothelial migration of lymphocytes are central events in the development of multiple sclerosis (MS). Autoreactive T cells are major players in MS pathogenesis, which are rapidly depleted following alemtuzumab treatment. This modulation, in turn, inhibits CNS inflammation, but alemtuzumab's effect on T cell migration into the CNS has been less studied. Human brain endothelial cells were stimulated with pro-inflammatory cytokines to mimic an inflamed BBB in vitro. Peripheral blood mononuclear cells from healthy controls, untreated or alemtuzumab-treated patients with relapsing-remitting MS (RRMS) were added to the BBB model to assess their transmigratory capacity. Here, the migration of CD4⁺ effector memory T (T^EM) and CD8⁺ central memory T (T^CM) cells across the BBB was impaired in alemtuzumab-treated patients. Naïve T (T^naïve) cells were unable to migrate across all groups. CD38 was lowly expressed on CD8⁺ T^CM cells, particularly for RRMS patients, compared to CD8⁺ T^naïve cells. CD62L expression was lower on CD4⁺ T^EM cells than CD4⁺ T^naïve cells and decreased further in alemtuzumab-treated patients. These data suggest that repopulated memory T cells are phenotypically different from naïve T cells, which may affect their transmigration across the BBB in vitro.

Keywords: T cells; alemtuzumab; blood–brain barrier; multiple sclerosis; trans-endothelial migration.

Abstract

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