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.
Highlights
Palatine tonsils and inflammatory diseasesThe palatine tonsils are located at the entrance of the upper aerodigestive tract for immune protection against ingested and inhaled pathogens
T-cell function in tonsil inflammation involving sequential density gradient centrifugation followed by automated magnetic separation using the autoMACSPro system and anti-CD4/CD8 beads for positive selection [17]
We observed no significant differences in the total numbers or in the CD4/CD8 ratios between tonsils of the various patient groups, suggesting that the various infection scenarios did not translate to large expansion or contraction of resident T-cell compartments
Summary
The palatine tonsils are located at the entrance of the upper aerodigestive tract for immune protection against ingested and inhaled pathogens. Immune protection in this area depends on both innate nonspecific defense mechanism and adaptive specific immune reactions. In particular, are present in high numbers in palatine tonsils and are largely located in the extra-follicular spaces [1]. Given their lymphoid nature and as supported by a number of immunological studies it has been proposed that tonsils are inductive sites for humoral and cell-mediated immune responses [2]. This issue is of high clinical relevance in the light of the high numbers of tonsillectomy surgeries performed as the result of various types of infectious complications
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