Steady-state antigen scavenging, cross-presentation, and CD8+ T cell priming: A new role for lymphatic endothelial cells

Sachiko Hirosue, Efthymia Vokali, Vidya R. Raghavan, Marcela Rincon-Restrepo, Amanda Lund, Patricia Corthésy-Henrioud, Francesca Capotosti, Cornelia Halin Winter, Stéphanie Hugues, Melody A. Swartz

Research output: Contribution to journalArticle

79 Citations (Scopus)

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 crosspresentation 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.

Original languageEnglish (US)
Pages (from-to)5002-5011
Number of pages10
JournalJournal of Immunology
Volume192
Issue number11
DOIs
StatePublished - Jun 1 2014
Externally publishedYes

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Cross-Priming
Endothelial Cells
T-Lymphocytes
Antigens
Lymph Nodes
Peripheral Tolerance
Endoplasmic Reticulum
Dendritic Cells
Interleukin-2
Drainage
Leukocytes
Cell Proliferation
Apoptosis
Ligands
Phenotype

ASJC Scopus subject areas

  • Immunology

Cite this

Hirosue, S., Vokali, E., Raghavan, V. R., Rincon-Restrepo, M., Lund, A., Corthésy-Henrioud, P., ... Swartz, M. A. (2014). Steady-state antigen scavenging, cross-presentation, and CD8+ T cell priming: A new role for lymphatic endothelial cells. Journal of Immunology, 192(11), 5002-5011. https://doi.org/10.4049/jimmunol.1302492

Steady-state antigen scavenging, cross-presentation, and CD8+ T cell priming : A new role for lymphatic endothelial cells. / Hirosue, Sachiko; Vokali, Efthymia; Raghavan, Vidya R.; Rincon-Restrepo, Marcela; Lund, Amanda; Corthésy-Henrioud, Patricia; Capotosti, Francesca; Winter, Cornelia Halin; Hugues, Stéphanie; Swartz, Melody A.

In: Journal of Immunology, Vol. 192, No. 11, 01.06.2014, p. 5002-5011.

Research output: Contribution to journalArticle

Hirosue, S, Vokali, E, Raghavan, VR, Rincon-Restrepo, M, Lund, A, Corthésy-Henrioud, P, Capotosti, F, Winter, CH, Hugues, S & Swartz, MA 2014, 'Steady-state antigen scavenging, cross-presentation, and CD8+ T cell priming: A new role for lymphatic endothelial cells', Journal of Immunology, vol. 192, no. 11, pp. 5002-5011. https://doi.org/10.4049/jimmunol.1302492
Hirosue, Sachiko ; Vokali, Efthymia ; Raghavan, Vidya R. ; Rincon-Restrepo, Marcela ; Lund, Amanda ; Corthésy-Henrioud, Patricia ; Capotosti, Francesca ; Winter, Cornelia Halin ; Hugues, Stéphanie ; Swartz, Melody A. / Steady-state antigen scavenging, cross-presentation, and CD8+ T cell priming : A new role for lymphatic endothelial cells. In: Journal of Immunology. 2014 ; Vol. 192, No. 11. pp. 5002-5011.
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AU - Lund, Amanda

AU - Corthésy-Henrioud, Patricia

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