title: Codominant Role of Interferon-γ- and Interleukin-17-Producing T Cells During Rejection in Full Facial Transplant Recipients.
abstract: Facial transplantation is a life-changing procedure for patients with severe composite facial defects. However, skin is the most immunogenic of all transplants, and better understanding of the immunological processes after facial transplantation is of paramount importance. Here, we describe six patients who underwent full facial transplantation at our institution, with a mean follow-up of 2.7 years. Seum, peripheral blood mononuclear cells, and skin biopsy specimens were collected prospectively, and a detailed characterization of their immune response (51 time points) was performed, defining 47 immune cell subsets, 24 serum cytokines, anti-HLA antibodies, and donor alloreactivity on each sample, producing 4269 data points. In a nonrejecting state, patients had a predominant T helper 2 cell phenotype in the blood. All patients developed at least one episode of acute cellular rejection, which was characterized by increases in interferon-γ/interleukin-17-producing cells in peripheral blood and in the allograft's skin. Serum monocyte chemotactic protein-1 level was significantly increased during rejection compared with prerejection time points. None of the patients developed de novo donor-specific antibodies, despite a fourfold expansion in T follicular helper cells at 1 year posttransplantation. In sum, facial transplantation is frequently complicated by a codominant interferon-γ/interleukin-17-mediated acute cellular rejection process. Despite that, medium-term outcomes are promising with no evidence of de novo donor-specific antibody development.
authors.affiliation: Schuster Transplantation Research Center, Brigham & Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Borges
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: J T
authors.initials: JT
authors.lastname: O'Malley
authors.affiliation: Division of Plastic Surgery, Department of Surgery, Brigham & Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: L
authors.initials: L
authors.lastname: Wo
authors.affiliation: Schuster Transplantation Research Center, Brigham & Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: N
authors.initials: N
authors.lastname: Murakami
authors.affiliation: Schuster Transplantation Research Center, Brigham & Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: B
authors.initials: B
authors.lastname: Smith
authors.affiliation: Schuster Transplantation Research Center, Brigham & Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: J
authors.initials: J
authors.lastname: Azzi
authors.affiliation: Schuster Transplantation Research Center, Brigham & Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: S
authors.initials: S
authors.lastname: Tripathi
authors.affiliation: Division of Plastic Surgery, Department of Surgery, Brigham & Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: J D
authors.initials: JD
authors.lastname: Lane
authors.affiliation: Division of Plastic Surgery, Department of Surgery, Brigham & Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: E M
authors.initials: EM
authors.lastname: Bueno
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: R A
authors.initials: RA
authors.lastname: Clark
authors.affiliation: Division of Transplant Surgery, Department of Surgery, Brigham & Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: S G
authors.initials: SG
authors.lastname: Tullius
authors.affiliation: Schuster Transplantation Research Center, Brigham & Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: A
authors.initials: A
authors.lastname: Chandraker
authors.affiliation: Program in Dermatopathology, Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: C G
authors.initials: CG
authors.lastname: Lian
authors.affiliation: Program in Dermatopathology, Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: G F
authors.initials: GF
authors.lastname: Murphy
authors.affiliation: Transplant Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: T B
authors.initials: TB
authors.lastname: Strom
authors.affiliation: Division of Plastic Surgery, Department of Surgery, Brigham & Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: B
authors.initials: B
authors.lastname: Pomahac
authors.affiliation: Schuster Transplantation Research Center, Brigham & Women's Hospital, Harvard Medical School, Boston, MA.|Department of Nephrology, Cleveland Clinic Florida, Weston, FL.
authors.forename: N
authors.initials: N
authors.lastname: Najafian
authors.affiliation: Schuster Transplantation Research Center, Brigham & Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: L V
authors.initials: LV
authors.lastname: Riella
mesh_terms: D000328:Adult; D054445:Facial Transplantation / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000175:diagnosis* / Q000209:etiology; D006085:Graft Survival / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology*; D007677:Kidney Function Tests; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D018417:Th1 Cells / Q000276:immunology*; D066027:Transplant Recipients
chemical_list: D020381:Interleukin-17; D007371:Interferon-gamma
keywords: T cell biology; basic (laboratory) research/science; clinical research/practice; immunobiology; immunosuppressant; rejection; rejection: T cell mediated (TCMR); vascularized composite and reconstructive transplantation