The Tonsil Lymphocyte Landscape in Pediatric Tonsil Hyperplasia and Obstructive Sleep Apnea

Carrasco, Anna; Sjölander, Isabella; Acker, Aline Van; Dernstedt, Andy; Fehrm, Johan; Forsell, Mattias N.E.; Friberg, Danielle; Mjösberg, Jenny; Rao, Anna

doi:10.3389/fimmu.2021.674080

Cited by 6 publications

(9 citation statements)

References 58 publications

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“…This is due to the difficulties in obtaining these lower airway samples from children, as well as limitations in sample volumes for research testing. However, we were able to obtain samples from a larger number of children for all other sample types (n=17-49), and these numbers are similar to or above that of other immunological studies using paediatric respiratory specimens 13, 16–18 . We also acknowledge that these samples were collected as part of clinically indicated procedures, which means that not all samples can be considered ‘healthy’.…”

Section: Discussionsupporting

confidence: 67%

A cross-tissue, age-specific flow cytometry reference for immune cells in the airways and blood of children

Shanthikumar,

Gubbels,

Davies

et al. 2024

Preprint

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Respiratory diseases are a common cause of morbidity and hospitalisation for children. Despite this, treatment options are limited and are often ineffective. The development of curative or disease-modifying treatments for children relies on a better understanding of underlying immunity in the early airway. To establish a flow cytometry reference for immune cells in the paediatric airway, we analysed 178 samples from 66 children aged between 1-15 years. This included five tissues of the upper (nasal brushings, palatine tonsils, adenotonsil) and lower (bronchial brushings, bronchoalveolar lavage (BAL)) airway, as well as whole blood for paired analysis of local and systemic immune response. Nasal, bronchial, and alveolar samples were analysed using a 17-plex antibody panel that captures cells of immune and epithelial lineage, while tonsil, adenoid, and blood samples were analysed using a 31-plex antibody panel that extensively phenotypes mononuclear immune cells. All protocols, panels, and data are openly available, to facilitate implementation in paediatric clinical laboratories. We provide age-specific cell reference data for infancy (0-2 years), preschool (3-5 years), childhood (6-10 years) and adolescence (11-15 years) for 37 cell populations. We show tissue-specific maturation of the airway immune system across childhood, further highlighting the importance of developing age-specific references of the paediatric airway. Intra-individual, cross-tissue analysis of paired samples revealed marked correlation in immune cell proportions between paired nasal-bronchial samples, paired tonsil-adenoid samples, and paired adenoid-blood samples, which may have implications for clinical testing. Our study advances knowledge of airway immunity from infancy through to adolescence and provides an openly available control dataset to aid in interpretation of clinical findings in samples obtained from children with respiratory diseases.

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Section: Discussionsupporting

confidence: 67%

A cross-tissue, age-specific flow cytometry reference for immune cells in the airways and blood of children

Shanthikumar,

Gubbels,

Davies

et al. 2024

Preprint

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“…The anatomical position of tonsils makes them the first line defense against inhaled and ingested pathogens and prone to inflammation. Local inflammation in tonsils can become chronic and is linked to changes in lymphocyte populations in response to pro-inflammatory cytokines (66, 67). Specifically, B cells and ILCs are dysregulated in pediatric patients with chronic local inflammation, suggesting that NK cells could also be affected (66).…”

Section: Discussionmentioning

confidence: 99%

“…Local inflammation in tonsils can become chronic and is linked to changes in lymphocyte populations in response to pro-inflammatory cytokines (66, 67). Specifically, B cells and ILCs are dysregulated in pediatric patients with chronic local inflammation, suggesting that NK cells could also be affected (66). Increased localization of NK cell subsets to the interfollicular and parafollicular domain in the presence of local inflammation could be attributed to multiple factors.…”

Section: Discussionmentioning

confidence: 99%

Mapping human natural killer cell development in pediatric tonsil by imaging mass cytometry and high-resolution microscopy

Hegewisch-Solloa,

Melsen,

Ravichandran

et al. 2023

Preprint

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Natural killer (NK) cells develop from CD34+progenitors in a stage-specific manner defined by changes in cell surface receptor expression and function. Secondary lymphoid tissues, including tonsil, are sites of human NK cell development. Here we present new insights into human NK cell development in pediatric tonsil using cyclic immunofluorescence and imaging mass cytometry. We show that NK cell subset localization and interactions are dependent on NK cell developmental stage and tissue residency. NK cell progenitors are found in the interfollicular domain in proximity to cytokine-expressing stromal cells that promote proliferation and maturation. Mature NK cells are primarily found in the T-cell rich parafollicular domain engaging in cell-cell interactions that differ depending on their stage and tissue residency. The presence of local inflammation results in changes in NK cell interactions, abundance, and localization. This study provides the first comprehensive atlas of human NK cell development in secondary lymphoid tissue.

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“…Given the increase in activated populations we observe, it is possible that the expanded Tfh and CD8 + T cells we found in the tissue may develop in part as a result of bystander activation during the anti-viral response. Lastly, COVID-19convalescent participants underwent tonsillectomy for sleep disordered breathing or obstructive sleep apnea due to hypertrophy of the adenoids and/or tonsils, which may be an immunologic disorder 54 . Although control samples also came from individuals with the same conditions, it is possible that these chronic disease states influence the immune response to SARS-CoV-2.…”

Section: Discussionmentioning

confidence: 99%

Robust, persistent adaptive immune responses to SARS-CoV-2 in the oropharyngeal lymphoid tissue of children

Manthiram

Milanez-Almeida

et al. 2022

Preprint

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SARS-CoV-2 infection triggers adaptive immune responses from both T and B cells. However, most studies focus on peripheral blood, which may not fully reflect immune responses in lymphoid tissues at the site of infection. To evaluate both local and systemic adaptive immune responses to SARS-CoV-2, we collected peripheral blood, tonsils, and adenoids from 110 children undergoing tonsillectomy/adenoidectomy during the COVID-19 pandemic and found 24 with evidence of prior SARS-CoV-2 infection, including detectable neutralizing antibodies against multiple viral variants. We identified SARS-CoV-2-specific germinal center (GC) and memory B cells; single cell BCR sequencing showed that these virus-specific B cells were class-switched and somatically hypermutated, with overlapping clones in the adenoids and tonsils. Oropharyngeal tissues from COVID-19-convalescent children showed persistent expansion of GC and anti-viral lymphocyte populations associated with an IFN-γ-type response, with particularly prominent changes in the adenoids, as well as evidence of persistent viral RNA in both tonsil and adenoid tissues of many participants. Our results show robust, tissue-specific adaptive immune responses to SARS-CoV-2 in the upper respiratory tract of children weeks to months after acute infection, providing evidence of persistent localized immunity to this respiratory virus.

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The Tonsil Lymphocyte Landscape in Pediatric Tonsil Hyperplasia and Obstructive Sleep Apnea

Cited by 6 publications

References 58 publications

A cross-tissue, age-specific flow cytometry reference for immune cells in the airways and blood of children

A cross-tissue, age-specific flow cytometry reference for immune cells in the airways and blood of children

Mapping human natural killer cell development in pediatric tonsil by imaging mass cytometry and high-resolution microscopy

Robust, persistent adaptive immune responses to SARS-CoV-2 in the oropharyngeal lymphoid tissue of children

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