title: The Presence of HLA-E-Restricted, CMV-Specific CD8+ T Cells in the Blood of Lung Transplant Recipients Correlates with Chronic Allograft Rejection.
abstract: The human cytomegalovirus (CMV) immune evasion protein, UL40, shares an identical peptide sequence with that found in the leader sequence of many human leukocyte antigen (HLA)-C alleles and when complexed with HLA-E, can modulate NK cell functions via interactions with the CD94-NKG2 receptors. However the UL40-derived sequence can also be immunogenic, eliciting robust CD8+ T cell responses. In the setting of solid organ transplantation these T cells may not only be involved in antiviral immunity but also can potentially contribute to allograft rejection when the UL40 epitope is also present in allograft-encoded HLA. Here we assessed 15 bilateral lung transplant recipients for the presence of HLA-E-restricted UL40 specific T cells by tetramer staining of peripheral blood mononuclear cells (PBMC). UL40-specific T cells were observed in 7 patients post-transplant however the magnitude of the response varied significantly between patients. Moreover, unlike healthy CMV seropositive individuals, longitudinal analyses revealed that proportions of such T cells fluctuated markedly. Nine patients experienced low-grade acute cellular rejection, of which 6 also demonstrated UL40-specific T cells. Furthermore, the presence of UL40-specific CD8+ T cells in the blood was significantly associated with allograft dysfunction, which manifested as Bronchiolitis Obliterans Syndrome (BOS). Therefore, this study suggests that minor histocompatibility antigens presented by HLA-E can represent an additional risk factor following lung transplantation.
authors: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria, Australia.
authors: Lucy C
authors: LC
authors: Sullivan
authors: Department of Medicine, Monash University, Central Clinical School, The Alfred Centre, Commercial Road, Melbourne, Victoria, Australia; Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Commercial Road, Melbourne, Victoria, Australia.
authors: Glen P
authors: GP
authors: Westall
authors: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria, Australia.
authors: Jacqueline M L
authors: JM
authors: Widjaja
authors: Department of Medicine, Monash University, Central Clinical School, The Alfred Centre, Commercial Road, Melbourne, Victoria, Australia; Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Commercial Road, Melbourne, Victoria, Australia.
authors: Nicole A
authors: NA
authors: Mifsud
authors: Department of Medicine, Monash University, Central Clinical School, The Alfred Centre, Commercial Road, Melbourne, Victoria, Australia; Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Commercial Road, Melbourne, Victoria, Australia.
authors: Thi H O
authors: TH
authors: Nguyen
authors: Department of Medicine, Monash University, Central Clinical School, The Alfred Centre, Commercial Road, Melbourne, Victoria, Australia; Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Commercial Road, Melbourne, Victoria, Australia.
authors: Aislin C
authors: AC
authors: Meehan
authors: Department of Medicine, Monash University, Central Clinical School, The Alfred Centre, Commercial Road, Melbourne, Victoria, Australia; Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Commercial Road, Melbourne, Victoria, Australia.
authors: Tom C
authors: TC
authors: Kotsimbos
authors: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria, Australia.
authors: Andrew G
authors: AG
authors: Brooks
mesh_terms: D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology / Q000472:pathogenicity; D003602:Cytotoxicity, Immunologic; D005260:Female; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000097:blood / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D066027:Transplant Recipients; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology; D000097625:HLA-E Antigens
chemical_list: D015395:Histocompatibility Antigens Class I; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011948:Receptors, Antigen, T-Cell; D014764:Viral Proteins; D000097625:HLA-E Antigens; C404228:UL40 glycoprotein, Cytomegalovirus