title: Interpreting NK cell transcripts versus T cell transcripts in renal transplant biopsies.
abstract: NK cell transcripts are increased in biopsies with antibody-mediated rejection, whereas T cell transcripts are increased in T cell-mediated rejection. However, NK and T cells share many features, creating potential ambiguity. Therefore to estimate the NK- versus T cell transcript burdens separately, we defined nonoverlapping transcripts selective for NK cells (N = 4) or T cells (N = 5). We compared NK- versus T cell transcript burdens in microarrays from 403 kidney transplant biopsies (182 early, 221 late). In late biopsies, high NK-cell transcript expression was associated with antibody-mediated rejection, correlating with microvascular inflammation and donor specific HLA antibody. However, some early biopsies with T cell-mediated rejection had high NK-cell transcript expression, as well as T cell transcripts, without evidence of antibody-mediated rejection or DSA, correlating with interstitial inflammation and tubulitis. Both NK-cell and T cell transcripts were moderately increased in many kidneys with inflammation secondary to injury or atrophy scarring. These results support the distinct role of NK cells in late antibody-mediated rejection, but indicate a role for NK-transcript expressing cells (NK cells or T cells with NK features) both in T cell-mediated rejection and in inflammation associated with injury and atrophy scarring.
authors.affiliation: Department of Laboratory Medicine and Pathology, Division of Nephrology and Transplant Immunology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: L G
authors.initials: LG
authors.lastname: Hidalgo
authors.forename: J
authors.initials: J
authors.lastname: Sellares
authors.forename: B
authors.initials: B
authors.lastname: Sis
authors.forename: M
authors.initials: M
authors.lastname: Mengel
authors.forename: J
authors.initials: J
authors.lastname: Chang
authors.forename: P F
authors.initials: PF
authors.lastname: Halloran
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006084:Graft Rejection / Q000235:genetics* / Q000276:immunology; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D007518:Isoantibodies / Q000097:blood / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008833:Microcirculation / Q000235:genetics / Q000276:immunology; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012079:Renal Circulation / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007518:Isoantibodies; D012333:RNA, Messenger