title: Lymph node-derived lymphatic endothelial cells express functional costimulatory molecules and impair dendritic cell-induced allogenic T-cell proliferation.
abstract: Lymphatic endothelial cells (LECs) interact with different immune cells, including T cells within lymph nodes (LNs). However, direct interactions of LECs with immune cells have yet to be investigated. In vitro studies were performed to characterize primary cultures of human LECs derived from LNs in their capacity of interacting with T cells. The results show that LECs express HLA molecules and functional costimulatory molecules needed for T-cell activation. A direct binding of LECs and T cells was detected in cell cultures connected with a clustering of costimulatory molecules on the contact phase. LECs were also able to take up and process antigens. However, major histocompatibility complex class II(+) LECs fail to induce allogeneic T-cell proliferation. Interestingly, supernatants of IFN-γ activated LECs impair proliferation of T cells cocultured with allogeneic dendritic cells, suggesting an inhibitory role of LECs. Indoleamine 2,3 dioxygenase was identified as one inhibitory molecule, which may be responsible for the impaired CD4(+) T-cell proliferation. Our observations suggest a regulatory function for activated LECs on CD4(+) T cells, which may play a role in vivo in the maintenance of the critical balance between tolerance and recall responses.
authors.affiliation: Department of Vaccinology and Applied Microbiology, Helmholtz Centre of Infection Research, Braunschweig, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Nörder
authors.forename: Maximiliano G
authors.initials: MG
authors.lastname: Gutierrez
authors.forename: Sonia
authors.initials: S
authors.lastname: Zicari
authors.forename: Edoardo
authors.initials: E
authors.lastname: Cervi
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Caruso
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Guzmán
mesh_terms: D017951:Antigen Presentation; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D049109:Cell Proliferation; D054357:Chemokine CXCL10 / Q000096:biosynthesis; D018076:DNA, Complementary / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D018076:DNA, Complementary; D000949:Histocompatibility Antigens Class II; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma