Immune response in human tonsil tissue

Sammanfattning: Pathogenic mechanisms responsible for tonsillar hypertrophy (TH) in children sufferingfrom obstructive sleep apnea syndrome (OSAS) were studied and compared with childrenwith recurrent tonsillitis (RT) and infectious mononucleosis (IM), respectively.In an initial study the clinical consequences of OSAS caused by TH was investigated.Tonsillectomy resulted in improvement or normalization of symptoms as well as ofsleep recordings and dentofacial morphology. Bacterial cultures obtained from TH and RT groups showed colonization of Haemophilusinfluenzae and Streptococcus pyogenes in tonsillar crypts and in mucosal site inthe majority of cases, without evidence for ongoing viral infection. Immunohistochemicalstaining with the B-cell marker, L26, revealed that the follicles were significantlyincreased in size in TH as compared to RT. The immune responses were studied in these disorders, focusing on cytokine andeffector molecule expression at the local site. Assessment of IL-la, IL-IB,IL-2,IL-4,IL-6,L-8,IL-10, TNFa, TNFB and IFNy in cell suspension from tonsil tissue obtained fromTH and RT, was performed at the single-cell level by indirect immunofluorescence.A significant increased incidence of IL-1B, IL-6 and IL-2 producing cells was foundin the RT group compared to the TH group. We examined the presence of cytokines incryopreserved tonsil tissue from the same patients by immunohistochemical staining.The prevalence of IL-2, IFNy, IL-6 and IL-IO producing cells were increased in theRT group whereas IL-4 was upregulated in the TH group. We found that the cytokineproducing cells were strictly compartmentalized with excessive IL-I and TGFB producingcells just beneath the surface and crypt epithelium. The immunoregulatory cytokinesIL-2, IFNy, TNFB, G-CSF, GM-CSF, IL-4,1L-5 and IL-IO were produced in the T-cellrich extrafollicular area. In order to assess the immunocapacity of the tonsil cellsin the two clinical disorders, we used heat-inactivated Haemophilus influenzae andStreptococcus pyogenes to stimulate suspended tonsil cells in vitro. We found thatboth TH and RT responded with upregulation of IL-la, IL-IB, TNFa, IL-6,IL-8,IL-2,IFNy, TNFB and IL-IO production. However, we could not find any differences betweenthe two groups. Severe clinical symptoms in acute infectious mononucleosis are linked to the developmentof extensive cellular immune activation. EBV-antigen positive cells were found in17% of the B-cell population and co-localized to C D8+ T-cells in the extrafolliculararea in IM. An increased incidence of IL-IB,IL-2, IFNy, IL-IO and IL-12 producingcells characterized the IM tonsils when compared to RT. The effector molecules, CD95,Fas-ligand and perforin as well as the apoptotic process were also upregulated inIM but not in RT, and localized to the extrafollicular site. Thus, the cytotoxicresponse seems to be cruical for control of acute EBV infection. The localization of the immune response in tonsil tissue is visualized for thefirst time, illustrating the importance of the complexity of the local immune responsemechanisms in different diseases. The increase of IL-4 may be one explanation forthe enlarged follicles noticed in tonsillar hypertrophy. Key words: Tonsillar hypertrophy, reeurrent tonsillitis, infectious mononueleosis,cytokine, immune response. ISBN 91-628-2714-6