000201392 001__ 201392
000201392 005__ 20180913062647.0
000201392 0247_ $$2doi$$a10.4049/jimmunol.1302492
000201392 022__ $$a0022-1767
000201392 02470 $$2ISI$$a000337171800010
000201392 037__ $$aARTICLE
000201392 245__ $$aSteady-State Antigen Scavenging, Cross-Presentation, and CD8(+) T Cell Priming: A New Role for Lymphatic Endothelial Cells
000201392 269__ $$a2014
000201392 260__ $$aBethesda$$bAmer Assoc Immunologists$$c2014
000201392 300__ $$a10
000201392 336__ $$aJournal Articles
000201392 520__ $$aUntil 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.
000201392 700__ $$aHirosue, Sachiko$$uEcole Polytech Fed Lausanne, Inst Bioengn, CH-1015 Lausanne, Switzerland
000201392 700__ $$aVokali, Efthymia$$uEcole Polytech Fed Lausanne, Inst Bioengn, CH-1015 Lausanne, Switzerland
000201392 700__ $$aRaghavan, Vidya R.$$uEcole Polytech Fed Lausanne, Inst Bioengn, CH-1015 Lausanne, Switzerland
000201392 700__ $$aRincon-Restrepo, Marcela$$uEcole Polytech Fed Lausanne, Inst Bioengn, CH-1015 Lausanne, Switzerland
000201392 700__ $$aLund, Amanda W.$$uEcole Polytech Fed Lausanne, Inst Bioengn, CH-1015 Lausanne, Switzerland
000201392 700__ $$aCorthesy-Henrioud, Patricia$$uEcole Polytech Fed Lausanne, Inst Bioengn, CH-1015 Lausanne, Switzerland
000201392 700__ $$aCapotosti, Francesca$$uEcole Polytech Fed Lausanne, Inst Bioengn, CH-1015 Lausanne, Switzerland
000201392 700__ $$aWinter, Cornelia Halin$$uSwiss Fed Inst Technol Zurich ETHZ, Inst Pharmaceut Sci, Zurich, Switzerland
000201392 700__ $$aHugues, Stephanie$$uUniv Geneva, Ctr Med Univ, Fac Med, Dept Pathol & Immunol, Geneva, Switzerland
000201392 700__ $$0242992$$aSwartz, Melody A.$$g160091$$uEcole Polytech Fed Lausanne, Inst Bioengn, CH-1015 Lausanne, Switzerland
000201392 773__ $$j192$$k11$$q5002-5011$$tJournal Of Immunology
000201392 909C0 $$0252115$$pLLCB$$xU11747
000201392 909CO $$ooai:infoscience.tind.io:201392$$particle
000201392 937__ $$aEPFL-ARTICLE-201392
000201392 973__ $$aEPFL$$rREVIEWED$$sPUBLISHED
000201392 980__ $$aARTICLE