title: Gene expression changes in HLA mismatched mixed lymphocyte cultures reveal genes associated with allorecognition.
abstract: Human leucocyte antigen (HLA) compatibility is the main factor determining the occurrence of graft-vs-host disease (GVHD) in patients. It has also been shown that minor histocompatibility antigen differences as well as genetic polymorphisms that are not sequenced by standard methodology for HLA typing can play a role. We used mixed lymphocyte cultures (MLCs) as a functional cellular test and investigated gene expression changes driven by HLA incompatibility in an effort to better understand the mechanisms involved in the disease. Gene expression profile of HLA matched and HLA mismatched MLC identified differentially regulated genes and pathways. We found that a great number of genes related to immune function were differentially regulated; these genes were also found to be associated with GVHD and graft rejection. The majority of differentially regulated genes were interferon-gamma (IFNγ)-inducible genes and IFNγ neutralisation in MLCs abrogated their induction. The microRNA-155, a recently identified target for acute GVHD (aGVHD), was also found to be significantly induced in HLA mismatched MLC but not in the matched setting and its induction was not diminished by blocking IFNγ. In this proof-of-principle study we show gene expression changes in mismatched MLC that represent alloreactive responses, correlate with markers involved in GVHD and can potentially be useful in the study of the biological processes involved in this disease.
authors: The Center for the Study of Haematological Malignancies, Nicosia, Cyprus.
authors: V
authors: V
authors: Nicolaidou
authors: C
authors: C
authors: Stylianou
authors: L
authors: L
authors: Koumas
authors: G S
authors: GS
authors: Vassiliou
authors: K B
authors: KB
authors: Bodman-Smith
authors: P
authors: P
authors: Costeas
mesh_terms: D057134:Antibodies, Neutralizing / Q000494:pharmacology; D018925:Chemokines / Q000235:genetics / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology*; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000473:pathology; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology / Q000473:pathology; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D008954:Models, Biological; D015398:Signal Transduction; D014019:Tissue Donors
chemical_list: D057134:Antibodies, Neutralizing; D018925:Chemokines; D006680:HLA Antigens; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D007371:Interferon-gamma
keywords: graft-vs-host; human leucocyte antigen; interferon-gamma; microRNA-155; mixed lymphocyte culture