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Immune cells in human pharyngeal and palatine tonsils and in the uvula: tissue distribution, cellular composition and functional properties
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
1999 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The adenoid (pharyngeal tonsil), the palatine tonsils and the uvula are strategically located at the entrance of the upper airodigestive tract. By virtue of their location they are incessantly exposed to inhaled and ingested antigens. Severe nasal obstruction, otitis media with effusion, recurrent tinsillitis and obstructive airways during sleep are conditions often due to diseases in these organs.

To advance our knowledge about the etiology and pathogenesis of these diseases, we have compared immune cell composition, cytokine expression and microbial colonisation in adenoids from children with hypertrophic obstructive adenoid (HOA) and chronically infected adenoid (CIA). Similarly, we compared immune cell composition in palatine tonsils from children with idiopathic tonsillar hypertrophy and recurrent tonsillitis. Finally, we wanted to characterise the human uvula from an immunological point of view, which had previously not been done. Its composition and distribution of immune cells, its cytokine profile, connective tissue elements and ultrastructure was studied.

When comparing adenoids from children with HOA and CIA, the most striking finding was their similarity. A cytokine profile that was independent of diagnosis but seemed characteristic for the adenoid emerged. T cell expression of IL-5 and TGF-β1 but not IL-4 suggested an ongoing humoral response driven by a "mucosal TH2" cell. αβ T cells also expressed TNF-α, IFN-γ and IL-2, indicating a concomitant cell mediated response. Cell mediated immune responses often reflect viral infection. In line with this, adenovirus DNA was found in 80% of the adenoid samples. Furthermore, IL-6, IL-8 and TNF-α expressed in the non-T cell fraction suggested that the tissue macrophages were activated. TNF-α, IFN-γ and TGF-β1 were expressed by γδ T cells. The following differences between HOA and CIA were however, noted: i) most intraepithelial lymphocytes were CD8+ γδ T cells in HOA, while CD8+ αβ T cells dominated intraepithelially in CIA; ii) the number of follicles was twice as high in CIA as in HOA; iii) there were signifacantly more granulocytes in the interfollicular area in CIA than in HOA; iv)IL-6 mRNA expressing γδ T cells were only found in HOA and v) there was a tendency of higher TNF-α mRNA levels in non-T cells of CIA compared to HOA. The following scenarios emerge: in CIA there appears to be an inadequate first line of defence, with a low frequency of intraepithelial γδ T cells and a high frequency of cytotoxic CD8+ αβ T cells eliminating infected epithelial cells. Togehter, these two conditions cause a "leaky" epithelium, allowing infiltration of microbes into the underlying tissue and subsequent recruitment of granulocytes and follicle formation initiated by activated macrophages. In HOA, activated intraepithelial γδ T cells appear to be involved in antimicrobial defence reactions and surveillance of the epithelium.

The difference in leukocyte profiles between tonsils from patients subjected to surgery due to idiopathic tonsillar hypertrophy or recurrent tonsillitis was limited to the surface epithelium. CD8+ γδ T cells utilising the unusual combination Vδ1/Vγ9 in their T cell receptor constituted the majority of intraepithelial lymphocytes in both groups. However, the frequency of these cells was significantly higher in recurrent tonsillitis. These results suggest that CD8+ Vδ1/Vγ9+ γδ T cells are characteristic of palatine tonsils and selectively expanded in recurrent tonsillitis. These γδ T cells may be involved in clearing infectious bacteria at the surface of the tonsil.

Tissue macrophages, αβ T cells, γδ T cells, mast cells and B cells constituted, in declining order, the immune cell populations in the uvula. No fillicle-like structures were present. Most T cells had a CD8+ CD28-TCR-αβ+ phenotype, suggesting a down-regulatory function. Production of the down-regulatory cytokine TGF-β was also noted. This is consistent with the hypothesis that the uvula contributes to the development of mucosal tolerance. Furthermore, the uvula seems to be protected from pathogens penetrating the internal milieu by a subepithelial barrier of γδ T cells and macrophages. TNF-α secreting immune cells were found at this location. TNF-α and TGF-β may cause tissue fibrosis, TNF-α indirectly by stimulating mast cells to release histamine. Tissue fibrosis in conjunction with water binding to hyaluronan present in the connective tissue is the most likely explanation for the observed enlargement of the uvula in patients with sleeping disorders.

Place, publisher, year, edition, pages
Umeå: Umeå universitet , 1999. , 71 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 607
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:umu:diva-79111ISBN: 91-7191-629-6 (print)OAI: oai:DiVA.org:umu-79111DiVA: diva2:639515
Public defence
1999-10-01, Sal D, Tandläkarhögskolan, Norrlands universitetssjukhus, Umeå, 10:00
Opponent
Supervisors
Available from: 2013-08-08 Created: 2013-08-08 Last updated: 2013-08-08Bibliographically approved
List of papers
1. Abundance of intraepithelial gamma delta T cells in hypertrophic obstructive but not in chronically infected adenoids
Open this publication in new window or tab >>Abundance of intraepithelial gamma delta T cells in hypertrophic obstructive but not in chronically infected adenoids
1996 (English)In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 106, no 2, 396-403 p.Article in journal (Refereed) Published
Abstract [en]

Using quantitative morphometric analysis of immunohistochemically stained tissue sections we compared hypertrophic obstructive adenoids (HOA, n = 10) from children without middle ear disease with chronically infected adenoids (CIA, n = 10) from children with middle ear disease. gamma delta T cell receptor (TCR)+ cells constituted the dominating T cell population in the surface epithelium of HOA, while alpha beta TCR+ cells were the dominating intraepithelial T cell population in CIA. Intraepithelially CD8+ cells dominated over CD4+ cells in both diseases. Intraepithelially B cells were not detected. The cellular composition of follicles, with B cells dominating followed by activated CD4+ alpha beta TCR+ cells, was the same in both groups. However, the number of follicles in CIA was twice as many as in HOA. In the deeper interfollicular areas granulocytes were more abundant in CIA than in HOA. The latter two findings suggest a more pronounced inflammatory response in the adenoids of patients with middle ear disease. There was no significant difference with regard to pathogenic bacterial strains colonizing the adenoid surface when comparing the two patient groups. These results suggest that in patients with HOA gamma delta TCR+ T cells help to maintain the integrity of the surface epithelium, thereby preserving its protective function. On the basis of our results we speculate that CIA have a malfunctioning defence, thereby facilitating long-standing infections deep in the adenoid. This may be the main reason for development of middle ear disease and an indication for adenoidectomy in patients with CIA.

National Category
Immunology
Identifiers
urn:nbn:se:umu:diva-67901 (URN)10.1046/j.1365-2249.1996.d01-825.x (DOI)8918590 (PubMedID)
Available from: 2013-04-07 Created: 2013-04-07 Last updated: 2017-12-06Bibliographically approved
2. The cytokine profile of T cells in the pharyngeal tonsil of children
Open this publication in new window or tab >>The cytokine profile of T cells in the pharyngeal tonsil of children
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-79110 (URN)
Available from: 2013-08-08 Created: 2013-08-08 Last updated: 2013-08-08Bibliographically approved
3. The surface epithelium of recurrent infected palatine tonsils is rich in gammadelta T cells
Open this publication in new window or tab >>The surface epithelium of recurrent infected palatine tonsils is rich in gammadelta T cells
1998 (English)In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 111, no 1, 36-47 p.Article in journal (Refereed) Published
Abstract [en]

Using a large panel of MoAbs in quantitative morphometric analysis of immunohistochemically stained tissue sections, we compared the frequency and distribution of immune cells in palatine tonsils from patients with recurrent tonsillitis (RT) and patients with idiopathic tonsillar hypertrophy (ITH). We found that differences between the two patient groups in leucocyte populations were limited to the surface epithelium, whereas the cellular composition of interfollicular and follicular areas was similar. Most intraepithelial lymphocytes were CD8+ T cells in both groups. However, the number of intraepithelial T cells was significantly higher in RT compared with ITH. This was due to a selective increase in the number of intraepithelial CD8+ gammadelta T cells utilizing Vdelta1 and Vgamma9. In both patient groups the majority of the intraepithelial gammadelta T cells expressed Vdelta1 and Vgamma9. Subepithelially, gammadelta T cells utilizing Vgamma9 dominated over cells utilizing Vgamma8, while equal proportions expressed Vdelta1 and Vdelta2. These results suggest that cells utilizing the otherwise rare combination Vdelta1/Vgamma9 in their T cell receptors (TCR) may constitute a major gammadelta T cell population in palatine tonsils and are probably reactive to antigens specific to the tonsillar milieu. Furthermore, they indicate that preferentially this gammadelta T cell subpopulation is involved in immune reactions within the surface epithelium in RT. We speculate that gammadelta T cells are involved in clearing infectious bacteria at the tonsillar surface and in limiting inflammatory responses in the tonsils. Both local expansion and infiltration of blood cells probably contribute to the high numbers of gammadelta T cells in RT patients.

National Category
Immunology
Identifiers
urn:nbn:se:umu:diva-68018 (URN)10.1046/j.1365-2249.1998.00446.x (DOI)9472659 (PubMedID)
Available from: 2013-04-10 Created: 2013-04-10 Last updated: 2017-12-06Bibliographically approved
4. Human uvula: characterization of resident leukocytes and local cytokine production
Open this publication in new window or tab >>Human uvula: characterization of resident leukocytes and local cytokine production
2000 (English)In: Annals of Otology, Rhinology and Laryngology, ISSN 0003-4894, E-ISSN 1943-572X, Vol. 109, no 5, 488-496 p.Article in journal (Refereed) Published
Abstract [en]

Upper airway infections often lead to macroscopic changes in the architecture of the uvula. Using immunomorphometric analysis, we investigated the frequency and distribution of immune cells and of cytokine-producing cells in uvular samples. Tissue macrophages, alphabeta T cells, gammadelta T cells, and B cells were, in declining order, the main cell populations. Gammadelta T cells and B cells exhibited reciprocal localization, with almost all gammadelta T cells residing in the vicinity of the epithelium, and all B cells in the glandular area. The presence of cells expressing the suppressor phenotype CD8+CD28- alphabeta T cells is suggested. Fifteen to twenty-five percent of the immune cells expressed the down-regulatory cytokine tumor growth factor beta. Most macrophages were located subepithelially, in the vicinity of the basal lamina. The composition and cytokine profile of leukocytes in the tissue suggest that the uvula may be a site, additional to the jejunal mucosa, for induction of mucosal tolerance to inhaled and ingested antigens. Concomitantly, the uvula appears to be protected from invasion of microbial pathogens by a subepithelial barrier of macrophages and gammadelta T cells.

National Category
Otorhinolaryngology
Identifiers
urn:nbn:se:umu:diva-68023 (URN)10823479 (PubMedID)
Available from: 2013-04-10 Created: 2013-04-10 Last updated: 2017-12-06Bibliographically approved
5. Structure of the human uvula
Open this publication in new window or tab >>Structure of the human uvula
1999 (English)In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 119, no 6, 712-717 p.Article in journal (Refereed) Published
Abstract [en]

Eleven uvular biopsies were investigated for their morphology, the presence of mast cells and the distribution of hyaluronan and its major ligand CD44. Three microanatomical sites--surface epithelium, subepithelial area and area of glands--were examined. The oral side of the uvula was covered by a 15-20 cell thick layer of keratinized/parakeratinized surface epithelium, firmly anchored to the underlying connective tissue by connective tissue papillae. The width of the intercellular spaces in the epithelium increased toward the basal lamina, a location that exhibited intense hyaluronan and anti-CD44 staining. Most mast cells were located in the vicinity of blood vessels, at which sites there was high staining intensity of hyaluronan. Tissue mast cells could also be observed in the connective tissue septa enclosing the acini. Glands and muscle fibres became more sparse from the proximal part of the uvula to the distal end, while the amount of connective tissue increased. The localization and architecture of connective tissue elements and mast cells are consistent with the ability of the uvula to resist mechanical stresses and to develop oedema and fibrosis, respectively.

National Category
Immunology
Identifiers
urn:nbn:se:umu:diva-68019 (URN)10.1080/00016489950180685 (DOI)10587007 (PubMedID)
Available from: 2013-04-10 Created: 2013-04-10 Last updated: 2017-12-06Bibliographically approved

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