TY - JOUR
T1 - Internalization and presentation of myelin antigens by the brain endothelium guides antigen-specific T cell migration
AU - Lopes Pinheiro, Melissa
AU - Kamermans, Alwin
AU - Garcia-Vallejo, Juan J.
AU - Hof, Bert van het
AU - Wierts, Laura
AU - O'Toole, Tom
AU - Boeve, Daniel
AU - Verstege, Marleen
AU - van der Pol, Susanne M. A.
AU - Van Kooyk, Yvette
AU - de Vries, Helga E.
AU - Unger, Wendy W. J.
PY - 2016/6/23
Y1 - 2016/6/23
N2 - Trafficking of myelin-reactive CD4+ T-cells across the brain endothelium, an essential step in the pathogenesis of multiple sclerosis (MS), is suggested to be an antigen-specific process, yet which cells provide this signal is unknown. Here we provide direct evidence that under inflammatory conditions, brain endothelial cells (BECs) stimulate the migration of myelin-reactive CD4+ T-cells by acting as non-professional antigen presenting cells through the processing and presentation of myelin-derived antigens in MHC-II. Inflamed BECs internalized myelin, which was routed to endo-lysosomal compartment for processing in a time-dependent manner. Moreover, myelin/MHC-II complexes on inflamed BECs stimulated the trans-endothelial migration of myelin-reactive Th1 and Th17 2D2 cells, while control antigen loaded BECs did not stimulate T-cell migration. Furthermore, blocking the interaction between myelin/MHC-II complexes and myelin-reactive T-cells prevented T-cell transmigration. These results demonstrate that endothelial cells derived from the brain are capable of enhancing antigen-specific T cell recruitment.
AB - Trafficking of myelin-reactive CD4+ T-cells across the brain endothelium, an essential step in the pathogenesis of multiple sclerosis (MS), is suggested to be an antigen-specific process, yet which cells provide this signal is unknown. Here we provide direct evidence that under inflammatory conditions, brain endothelial cells (BECs) stimulate the migration of myelin-reactive CD4+ T-cells by acting as non-professional antigen presenting cells through the processing and presentation of myelin-derived antigens in MHC-II. Inflamed BECs internalized myelin, which was routed to endo-lysosomal compartment for processing in a time-dependent manner. Moreover, myelin/MHC-II complexes on inflamed BECs stimulated the trans-endothelial migration of myelin-reactive Th1 and Th17 2D2 cells, while control antigen loaded BECs did not stimulate T-cell migration. Furthermore, blocking the interaction between myelin/MHC-II complexes and myelin-reactive T-cells prevented T-cell transmigration. These results demonstrate that endothelial cells derived from the brain are capable of enhancing antigen-specific T cell recruitment.
U2 - https://doi.org/10.7554/eLife.13149
DO - https://doi.org/10.7554/eLife.13149
M3 - Article
C2 - 27336724
SN - 2050-084X
VL - 5
JO - eLife
JF - eLife
M1 - e13149
ER -