Expression and release of soluble HLA-E is an immunoregulatory feature of endothelial cell activation.
Human leukocyte antigen (HLA)-E belongs, with HLA-G and HLA-F, to the non-classic major histocompatibility complex (MHC) class I (Ib) molecules, broadly defined by a limited polymorphism and a restricted pattern of cellular expression. In contrast to HLA-G, the expression and function of HLA-E and HLA-F in physiologic and pathologic processes remain poorly established. In the present study, we show that HLA-E protein expression in normal human nonlymphoid organs is mainly restricted to endothelial cells (ECs). HLA-E is also basally expressed by B and T lymphocytes, natural killer (NK) cells and by macrophages. We demonstrate that tumor necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), and interferon gamma (IFNgamma) up-regulate the cell-surface expression of HLA-E on ECs in vitro and induce the release of soluble HLA-E (sHLA-E). HLA-E up-regulation protects IFN-gamma-activated ECs from NK-mediated cell lysis, while sHLA-E protects bystander cells. Finally, sHLA-E is not detected in normal sera, and increased serum levels correlate with disease activity in patients with antineutrophil cytoplasmic antibody-associated systemic vasculitis. Thus, HLA-E expression and release of sHLA-E are features of EC activation and emphasize immunoregulatory functions of the endothelium. The present identification of soluble HLA-E molecules may have important implications in understanding the pathogenesis of immune-mediated vascular diseases and for the diagnosis and monitoring of patients.
Coupel
Stéphanie
S
Institut National de la Santé et de la Recherche Médicale, Unit 643, Institut de Transplantation et de Recherche en Transplantation, Nantes, France.
Moreau
Anne
A
Hamidou
Mohamed
M
Horejsi
Vaclav
V
Soulillou
Jean-Paul
JP
Charreau
Béatrice
B
D001483:Base Sequence; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D017931:DNA Primers / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D006680:HLA Antigens / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000276:immunology; D007962:Leukocytes / Q000276:immunology; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000378:metabolism; D011247:Pregnancy; D011971:Receptors, Immunologic / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D012995:Solubility; D014657:Vasculitis / Q000276:immunology; D000097625:HLA-E Antigens
D016207:Cytokines; D017931:DNA Primers; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D000097625:HLA-E Antigens; C497869:KLRD1 protein, human