Mick Bailey

Human papillomavirus and head and neck cancer: a systematic review and meta-analysis

•It has been suggested that the link between human papillomavirus (HPV) and head and neck squamous cell carcinoma (HNSCC) is specific to carcinoma of the tonsil.

Expression of major histocompatibility complex class II antigens on normal porcine intestinal endothelium.

A novel monoclonal antibody (MIL 11) specific for an antigen expressed on porcine endothelial cells is described. The antigen recognized by MIL 11 is most strongly expressed in the intestine but is also expressed on the capillary endothelium of a wide range of tissues. Using two‐ and three‐colour immunofluorescence microscopy we demonstrated the extensive coexpression of MIL 11 and major histocompatibility complex (MHC) class II antigens on normal porcine capillary endothelium in the intestine, trachea, thymus and small veins, while endothelium of large vessels and the heart were negative for MHC class II. In contrast to humans and rodents, available reagents do not detect MHC class II on the intestinal epithlium of pigs. However, porcine intestinal endothelium expressed both DR and DQ antigens. A population of strongly class II‐positive cells was also detected immediately adjacent to the endothelium in the lamina propria. Three‐colour immunofluorescence microscopy highlighted the close association between endothelium and intestinal CD4+ T cells. Lamina propria T cells were mainly MHC class II positive, whereas those in the epithelial compartment were MHC class II negative.

A Preclinical Model For Laryngeal Transplantation: Anatomy And Mucosal Immunology Of The Porcine Larynx

BACKGROUND A major step in translating work on laryngeal transplantation into clinical practice is the establishment of a preclinical model. We have investigated the anatomy and mucosal immunology of the porcine larynx in eight Minnesota Minipigs (12-37 weeks). METHODS Neck dissections were carried out and the vascular tree was mapped. Snap-frozen biopsies from epiglottis, supraglottis, glottis, and subglottis were prepared for conventional histology, immunohistochemistry (CD45), and single and two-color immunofluorescence (CD3, MHC-II, CD45). RESULTS The anatomy of the laryngeal skeleton was broadly similar to that of the human larynx. The blood supply is predominantly via the caudal thyroid vessels, with assistance from the cranial laryngeal artery. The porcine larynx is clearly highly immunologically active. Structured collections of leukocytes were found in the mucosal epithelium, around tubuloacinar glands, and occasionally in the submucosa. MHC-II and CD 3 cells were predominantly found within the epithelium. The highest densities of all cell types were observed in the epiglottis, tailing off caudally. The lowest densities were seen in the vocal cords. CONCLUSIONS The porcine larynx is both anatomically and immunologically similar to the human larynx and contains a high level of immunological organization. It presents an ideal preclinical model for laryngeal transplantation.

The larynx as an immunological organ: immunological architecture in the pig as a large animal model

The larynx is a mucosal organ positioned at the divergence of the respiratory and digestive tracts. It is exposed to a wide variety of environmental components, including foreign antigens, tobacco smoke, laryngopharyngeal reflux and pollutants. The mucosal immune system generates either active immune responses or tolerance, depending on the nature of the antigen and we hypothesize that the larynx is important organ for immunological decision‐making in the airway. Because the pig is an ideal large animal model in which to explore laryngological research questions, such as those relating to laryngeal transplantation, we investigated the normal mucosal immunology of the porcine larynx. Pig larynges and tracheae were processed and prepared for bright‐field microscopy and quantitative, multiple‐colour immunofluorescence histology using pig‐specific monoclonal antibodies. There was an abundance of immunologically active cells within the mucosa of the larynx and trachea of both the newborn and adult animal. Specifically, major histocompatibility complex class II (MHC class II+) cells, CD4+ and CD8+ cells were identified, although regional differences in numbers were apparent: specifically, the supraglottis contained fewer immunologically relevant cells than other sites sampled. There was a significant correlation between the numbers of MHC class II+ and CD4+ cells indicating co‐ordinate regulation and therefore functional local interactions. The presence of such an immunological structure suggests that the larynx may have important functions in respiratory immunology and that it may trigger strong alloresponses after laryngeal transplantation.

Differential major histocompatibility complex class II locus expression on human laryngeal epithelium

The survival of a laryngeal allograft will be dependent on the immunological composition of the donor larynx and, in particular, on the expression of major histocompatibility complex (MHC) class II antigens on professional and non‐professional antigen‐presenting cells. Laryngeal and tonsillar biopsies from normal individuals aged 18–78 years were processed and prepared for quantitative, multiple‐colour immunofluorescence using mouse antihuman monoclonal antibodies to human leucocyte antigen (HLA)‐DR, HLA‐DQ and CD45. The laryngeal epithelium expressed HLA‐DR locus products at variable levels, but expression of HLA‐DQ was virtually absent. Tonsillar epithelial cells expressed HLA‐DR at the basal layer only, while HLA‐DQ was similarly not expressed. In contrast, both HLA‐DR and ‐DQ locus products were present on lamina propria and intraepithelial leucocytes in both laryngeal and tonsillar mucosae, although at varying levels. The finding that laryngeal epithelial cells express MHC class II antigens has implications for the survival of laryngeal allografts and suggests that they may require significant immunomodulation. In addition, antigen presentation by epithelial cells has been hypothesized to contribute to the immunoregulatory function of mucosal tissues, and the finding that HLA‐DQ locus products are only expressed at low levels by laryngeal epithelium raises questions about the repertoire of peptides to which the mucosal immune system can respond.

Antigen-receptor V segment usage in mucosal T cells.

In the accepted model of lymphocyte intestinal homing, naïve T cells recirculate via organized lymphoid tissues, whilst induced effector/memory cells home to the intestinal mucosa. In order to assess the T‐cell‐receptor repertoire in the intestine and gut‐associated lymphoid tissue (GALT), spectratyping was performed on the proximal and the distal intestine, spleen and mesenteric lymph node tissue from six PVG rats. The products were analysed with an automated sequencer and statistical analyses were performed with hierarchical cluster analysis. This demonstrated the presence of a restricted T‐cell repertoire in the small intestine compared with that in the mesenteric lymph nodes and the spleen. It also demonstrated marked differences in repertoire between individual, fully inbred rats maintained under apparently identical conditions in the same cage and fed identical diets. In addition, this work demonstrated marked differences between repertoires in the proximal and the distal intestine. Such marked differences are likely to reflect the end result of increasing divergence over time produced by relatively subtle effects of environment and antigenic load. Equally, marked differences in repertoire between small intestinal segments within individual rats indicate selective recruitment or retention of specific clones, presumably antigen‐driven.