Immunology of Pediatric Tonsil Disorders

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications, trials & patents

Abstract

Over the past 5 years, we have obtained tonsil samples from over 60 patients with PFAPA, obstructive sleep apnea, and controls with craniofacial anomalies. We analyzed the immune cell profile using flow cytometry, gene expression in particular cell populations, and function of particular cells with stimulation studies. Through our analyses of the tonsils, we found that sorted CD4+ T cells from the tonsils of patients with PFAPA have increased expression of Th1 and Th17-related genes. Moreover, upon stimulation with PMA and ionomycin, effector CD4+ T cells in the tonsils produce more IFN-gamma and IL-17 than those from controls undergoing tonsillectomy for anatomic craniofacial deformities. These data support the functionality of the risk variants with identified in individuals with PFAPA. We have also found that OSA is an inflammatory disease of the palatine tonsils with enlarged germinal centers, more T follicular helper (Tfh) cells, and activated effector CD4+ T cells, CD8+ T cells, and NK cells. In addition, sorted CD4+ T cells have greater expression of TGF-beta-related genes. Interestingly, TGF-beta from tonsillar antigen-presenting cells (APCs) was recently shown to promote Tfh differentiation and production of CXCL13, which attracts B cells to germinal centers. We will further evaluate this hypothesis in the context of obstructive sleep apnea. Over the past year, we have collected over 100 tonsils and adenoids as part of a COVID-19 project and developed a comprehensive high dimensional flow cytometry for immunophenotyping.