The brain microvascular endothelium supports T cell proliferation and has potential for alloantigen presentation

Julie Wheway; Stephanie Obeid; Pierre-Olivier Couraud; Valery Combes; Georges E R Grau

doi:10.1371/journal.pone.0052586

The brain microvascular endothelium supports T cell proliferation and has potential for alloantigen presentation

PLoS One. 2013;8(1):e52586. doi: 10.1371/journal.pone.0052586. Epub 2013 Jan 8.

Authors

Julie Wheway¹, Stephanie Obeid, Pierre-Olivier Couraud, Valery Combes, Georges E R Grau

Affiliation

¹ Discipline of Pathology, Sydney Medical School, University of Sydney, Camperdown, New South Wales, Australia. [email protected]

Abstract

Endothelial cells (EC) form the inner lining of blood vessels and are positioned between circulating lymphocytes and tissues. Hypotheses have formed that EC may act as antigen presenting cells based on the intimate interactions with T cells, which are seen in diseases like multiple sclerosis, cerebral malaria (CM) and viral neuropathologies. Here, we investigated how human brain microvascular EC (HBEC) interact with and support the proliferation of T cells. We found HBEC to express MHC II, CD40 and ICOSL, key molecules for antigen presentation and co-stimulation and to take up fluorescently labeled antigens via macropinocytosis. In co-cultures, we showed that HBEC support and promote the proliferation of CD4(+) and CD8(+) T cells, which both are key in CM pathogenesis, particularly following T cell receptor activation and co-stimulation. Our findings provide novel evidence that HBEC can trigger T cell activation, thereby providing a novel mechanism for neuroimmunological complications of infectious diseases.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antigen Presentation
Brain / blood supply*
Brain / immunology*
CD40 Antigens / metabolism
Cell Line
Cell Proliferation
Coated Pits, Cell-Membrane / immunology
Coculture Techniques
Endothelial Cells / immunology
Histocompatibility Antigens Class II / metabolism
Humans
Inducible T-Cell Co-Stimulator Ligand / metabolism
Isoantigens / metabolism
Lymphocyte Activation
Microvessels / cytology
Microvessels / immunology*
Pinocytosis / immunology
T-Lymphocytes / cytology*
T-Lymphocytes / immunology*

Substances

CD40 Antigens
Histocompatibility Antigens Class II
ICOSLG protein, human
Inducible T-Cell Co-Stimulator Ligand
Isoantigens

Grants and funding

The study was funded by the National Health and Medical Research Council of Australia (http://www.nhmrc.gov.au/) project grants 1009914 and 571014 to VC and GEG; 1028241 to JW, VC and GEG; and 1022368 to GEG; fellowship 571397 to JW. Support was also provided through Rebecca L. Cooper Foundation equipment grants (http://www.cooperfoundation.org.au/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.