PMID- 26302084 OWN - NLM STAT- MEDLINE DCOM- 20160517 LR - 20231213 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 10 IP - 8 DP - 2015 TI - The Presence of HLA-E-Restricted, CMV-Specific CD8+ T Cells in the Blood of Lung Transplant Recipients Correlates with Chronic Allograft Rejection. PG - e0135972 LID - 10.1371/journal.pone.0135972 [doi] LID - e0135972 AB - 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. FAU - Sullivan, Lucy C AU - Sullivan LC AD - Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria, Australia. FAU - Westall, Glen P AU - Westall GP AD - 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. FAU - Widjaja, Jacqueline M L AU - Widjaja JM AD - Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria, Australia. FAU - Mifsud, Nicole A AU - Mifsud NA AD - 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. FAU - Nguyen, Thi H O AU - Nguyen TH AD - 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. FAU - Meehan, Aislin C AU - Meehan AC AD - 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. FAU - Kotsimbos, Tom C AU - Kotsimbos TC AD - 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. FAU - Brooks, Andrew G AU - Brooks AG AD - Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria, Australia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150824 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Histocompatibility Antigens Class I) RN - 0 (NK Cell Lectin-Like Receptor Subfamily D) RN - 0 (Receptors, Antigen, T-Cell) RN - 0 (UL40 glycoprotein, Cytomegalovirus) RN - 0 (Viral Proteins) SB - IM MH - Adult MH - Aged MH - CD8-Positive T-Lymphocytes/immunology MH - Cytomegalovirus/immunology/pathogenicity MH - *Cytotoxicity, Immunologic MH - Female MH - Graft Rejection/genetics/immunology MH - Histocompatibility Antigens Class I/blood/*immunology MH - Humans MH - Killer Cells, Natural/immunology MH - Lung Transplantation/*adverse effects MH - Male MH - Middle Aged MH - NK Cell Lectin-Like Receptor Subfamily D/genetics/immunology MH - Receptors, Antigen, T-Cell/genetics/immunology MH - T-Lymphocytes, Cytotoxic/*immunology MH - Transplant Recipients MH - Viral Proteins/genetics/immunology MH - HLA-E Antigens PMC - PMC4547726 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2015/08/25 06:00 MHDA- 2016/05/18 06:00 PMCR- 2015/08/24 CRDT- 2015/08/25 06:00 PHST- 2015/04/26 00:00 [received] PHST- 2015/07/28 00:00 [accepted] PHST- 2015/08/25 06:00 [entrez] PHST- 2015/08/25 06:00 [pubmed] PHST- 2016/05/18 06:00 [medline] PHST- 2015/08/24 00:00 [pmc-release] AID - PONE-D-15-18106 [pii] AID - 10.1371/journal.pone.0135972 [doi] PST - epublish SO - PLoS One. 2015 Aug 24;10(8):e0135972. doi: 10.1371/journal.pone.0135972. eCollection 2015.