| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Lund, Amanda W. Raghavan, Vidya R. Swartz, Melody A. Rincon-Restrepo, Marcela Hugues, Stéphanie Vokali, Efthymia Capotosti, Francesca Hirosue, Sachiko Halin Winter, Cornelia Corthésy-Henrioud, Patricia |
| Description |
Author Affiliation: Hirosue S ( Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland); Vokali E ( Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland); Raghavan VR ( Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland); Rincon-Restrepo M ( Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland); Lund AW ( Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland); Corthésy-Henrioud P ( Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland); Capotosti F ( Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland); Halin Winter C ( Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology Zürich (ETHZ), Zürich, Switzerland); Hugues S ( Department of Pathology and Immunology, Faculty of Medicine, Centre Médical Universitaire, Université de Genève, Geneva, Switzerland); Swartz MA ( Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland) |
| Abstract |
Until recently, the known roles of lymphatic endothelial cells (LECs) in immune modulation were limited to directing immune cell trafficking and passively transporting peripheral Ags to lymph nodes. Recent studies demonstrated that LECs can directly suppress dendritic cell maturation and present peripheral tissue and tumor Ags for autoreactive T cell deletion. We asked whether LECs play a constitutive role in T cell deletion under homeostatic conditions. In this study, we demonstrate that murine LECs under noninflamed conditions actively scavenge and cross-present foreign exogenous Ags to cognate CD8(+) T cells. This cross-presentation was sensitive to inhibitors of lysosomal acidification and endoplasmic reticulum-golgi transport and was TAP1 dependent. Furthermore, LECs upregulated MHC class I and the PD-1 ligand PD-L1, but not the costimulatory molecules CD40, CD80, or CD86, upon Ag-specific interactions with CD8(+) T cells. Finally, Ag-specific CD8(+) T cells that were activated by LECs underwent proliferation, with early-generation apoptosis and dysfunctionally activated phenotypes that could not be reversed by exogenous IL-2. These findings help to establish LECs as APCs that are capable of scavenging and cross-presenting exogenous Ags, in turn causing dysfunctional activation of CD8(+) T cells under homeostatic conditions. Thus, we suggest that steady-state lymphatic drainage may contribute to peripheral tolerance by delivering self-Ags to lymph node-resident leukocytes, as well as by providing constant exposure of draining peripheral Ags to LECs, which maintain tolerogenic cross-presentation of such Ags. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| DOI |
10.4049/jimmunol.1302492 |
| Journal |
The Journal of Immunology |
| Issue Number |
11 |
| Volume Number |
192 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2014-06-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Antigen Presentation Physiology Antigen-presenting Cells Immunology Antigens Cd8-positive T-lymphocytes Endothelial Cells Histocompatibility Antigens Class I Animals Cytology Genetics Antigens, Cd274 Cell Line, Transformed Cross Reactions Interleukin-2 Mice Mice, Knockout Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
