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Functional characterization of T-cells from palatine tonsils in patients with chronic tonsillitis.

ABSTRACT: The palatine tonsils, localized in the oropharynx, are easily accessible secondary lymphoid tissue in humans. Inflammation of the palatine tonsils, local and chronic in case of chronic tonsillitis (CT) or acute in the presence of a peritonsillar abscess (PTA), ranks among the most common diseases in otolaryngology. However, the functionality of tonsillar immune cells, notably T-cells, in the context of these immune pathologies is poorly understood. We have examined the functional status of human tonsillar T-cells in CT and compared it to the acute inflammatory setting of a PTA. Patients presenting with CT (n = 10) or unilateral PTA (n = 7) underwent bilateral tonsillectomy and a subgroup of 8 patients underwent additional blood sampling. T-cells were purified via automated magnetic selection and subjected to flow cytometry-based immunophenotyping. In addition, the response to T-cell receptor (TCR) stimulation was assessed at the level of proximal signaling, activation marker expression and proliferation. We observed no difference between the percentage of T helper (CD4(+)) cells from tonsil tissue in CT and PTA, but observed a trend towards a higher percentage of T helper cells in the blood of patients with PTA versus CT, probably reflecting an acute, systemic bacterial infection in the former cohort. Tonsils from CT harbored more PD-1(+) CD4(+) T-cells, pointing to T-cell exhaustion due to chronic infection. This notion was supported by functional studies that showed a tendency to weaker TCR responses of tonsillar T-cells from CT. Intriguingly, tonsillar T-cells recurrently featured a dampened response to T-cell receptor stimulation at the level of receptor proximal signaling steps compared to peripheral T-cells. In sum, our study documents distinct differences in tonsillar T-cell class distribution and function between the various pathological conditions. Our observations are consistent with the concept that tonsillar T-cells react to infections by eliciting specific immunological responses in chronic versus acute settings of inflammation.

SUBMITTER: Geißler K

PROVIDER: S-EPMC5587326 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Functional characterization of T-cells from palatine tonsils in patients with chronic tonsillitis.

Geißler Katharina K Markwart Robby R Requardt Robert Pascal RP Weigel Cynthia C Schubert Katja K Scherag André A Rubio Ignacio I Guntinas-Lichius Orlando O

PloS one 20170906 9

The palatine tonsils, localized in the oropharynx, are easily accessible secondary lymphoid tissue in humans. Inflammation of the palatine tonsils, local and chronic in case of chronic tonsillitis (CT) or acute in the presence of a peritonsillar abscess (PTA), ranks among the most common diseases in otolaryngology. However, the functionality of tonsillar immune cells, notably T-cells, in the context of these immune pathologies is poorly understood. We have examined the functional status of human ...[more]

PMID: 28877231

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Project description:BACKGROUND:Memory B cell (mBC) induction and maintenance is one of the keys to long-term protective humoral immunity. MBCs are fundamental to successful medical interventions such as vaccinations and therapy in autoimmunity. However, their lifestyle and anatomic residence remain enigmatic in humans. Extrapolation from animal studies serves as a conceptual basis but might be misleading due to major anatomical distinctions between species. METHODS AND FINDINGS:Multicolor immunofluorescence stainings on fixed and unfixed frozen tissue sections were established using primary antibodies coupled to haptens and secondary signal amplification. The simultaneous detection of five different fluorescence signals enabled the localization and characterization of human CD27+CD20+Ki67- mBCs for the first time within one section using laser scanning microscopy. As a result, human tonsillar mBCs were initially identified within their complex microenvironment and their relative location to naïve B cells, plasma cells and T cells could be directly studied and compared to the human splenic mBC niche. In all investigated tonsils (n = 15), mBCs appeared to be not only located in a so far subepithelial defined area but were also follicle associated with a previous undescribed gradual decline towards the follicular mantle comparable to human spleen. However, mBC areas around secondary follicles with large germinal centers (GCs) in tonsils showed interruptions and a general widening towards the epithelium while in spleen the mBC-containing marginal zones (MZ) around smaller GCs were relatively broad and symmetrical. Considerably fewer IgM+IgD+/- pre-switch compared to IgA+ or IgG+ post-switch mBCs were detected in tonsils in contrast to spleen. CONCLUSIONS:This study extends existing insights into the anatomic residence of human mBCs showing structural similarities of the superficial follicular area in human spleen and tonsil. Our data support the debate of renaming the human splenic MZ to 'superficial zone' in order to be aware of the differences in rodents and, moreover, to consider this term equally for the human palatine tonsil.

Project description:Acute otitis media (AOM), secretory otitis media (SOM), and acute pharyngotonsillitis are the most frequent reasons for visits to general practitioners, pediatricians, and otolaryngologists. Microbial colonization of the epithelial lining of Waldeyer's lymphatic tissues, consisting of the palatine tonsils, lingual tonsils, adenoids, and Eustachian tube tonsil, is a well-known clinical challenge during infancy due to frequent episodes of upper respiratory tract infections. However, no previous studies have investigated the combined role of the palatine tonsils and the adenoids as a reservoir for pathogens associated with SOM in small children. We analyzed the combined crypt microbiome of the palatine tonsils and adenoids from 14 small children with hyperplasia of the tonsils or adenoids and 14 small children with SOM using 16S rRNA gene pyrosequencing. Our study demonstrated a significant difference between the microbiome of the adenoids and that of the palatine tonsils in the two groups but not between the two anatomical locations within the two groups. In particular, the potential pathogens Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were almost exclusively found in the adenoids of both patient groups, indicating that the adenoids and not the palatine tonsils are the main reservoir for potential pathogens leading to AOM and SOM. IMPORTANCE Our findings that the microbiome differs between crypts of the adenoids and crypts of the palatine tonsils, including the relative abundances of potential pathogens such as Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis, may be the stepping stone for further investigation of individual microbiomes in a longitudinal design that includes recording of the fluctuating health status of the child. Such studies may have the potential to lead to new preventive measurements such as implantation of protective nonpathogens at the nasopharynx as an alternative to adenoidectomy.

Dataset Information

Functional characterization of T-cells from palatine tonsils in patients with chronic tonsillitis.

Publications

Functional characterization of T-cells from palatine tonsils in patients with chronic tonsillitis.

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