title: Laryngeal transplantation in minipigs: early immunological outcomes.
abstract: Despite recent tissue-engineering advances, there is no effective way of replacing all the functions of the larynx in those requiring laryngectomy. A recent clinical transplant was a success. Using quantitative immunofluorescence targeted at immunologically relevant molecules, we have studied the early (48 h and 1 week) immunological responses within larynxes transplantated between seven pairs of National Institutes of Health (NIH) minipigs fully homozygous at the major histocompatibility complex (MHC) locus. There were only small changes in expression of some molecules (relative to interindividual variation) and these were clearest in samples from the subglottic region, where the areas of co-expression of CD25(+) CD45RC(-) CD8(-) and of CD163(+) CD172(+) MHC-II(-) increased at 1 week after transplant. In one case, infiltration by recipient T cells was analysed by T cell receptor (TCR) Vβ spectratype analysis; this suggested that changes in the T cell repertoire occur in the donor subglottis mucosal tissues from day 0 to day 7, but that the donor and recipient mucosal Vβ repertoires remain distinct. The observed lack of strong immunological responses to the trauma of surgery and ischaemia provides encouraging evidence to support clinical trials of laryngeal transplantation, and a basis on which to interpret future studies involving mismatches.
authors.affiliation: Department of Clinical Sciences at South Bristol, University of Bristol, Bristol, UK. m.birchall@ucl.ac.uk
authors.forename: M A
authors.initials: MA
authors.lastname: Birchall
authors.forename: S M
authors.initials: SM
authors.lastname: Ayling
authors.forename: R
authors.initials: R
authors.lastname: Harley
authors.forename: P J
authors.initials: PJ
authors.lastname: Murison
authors.forename: R
authors.initials: R
authors.lastname: Burt
authors.forename: L
authors.initials: L
authors.lastname: Mitchard
authors.forename: A
authors.initials: A
authors.lastname: Jones
authors.forename: P
authors.initials: P
authors.lastname: Macchiarini
authors.forename: C R
authors.initials: CR
authors.lastname: Stokes
authors.forename: M
authors.initials: M
authors.lastname: Bailey
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D005260:Female; D019674:Genes, T-Cell Receptor beta; D007830:Larynx / Q000276:immunology / Q000473:pathology / Q000637:transplantation*; D008285:Major Histocompatibility Complex; D008297:Male; D023421:Models, Animal; D013552:Swine; D013556:Swine, Miniature / Q000235:genetics / Q000276:immunology* / Q000601:surgery*; D013997:Time Factors; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
chemical_list: D015703:Antigens, CD