Immune response in human tonsil tissue

Abstract

Pathogenic mechanisms responsible for tonsillar hypertrophy (TH) in children suffering from obstructive sleep apnea syndrome (OSAS) were studied and compared with children with 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 of sleep recordings and dentofacial morphology.

Bacterial cultures obtained from TH and RT groups showed colonization of Haemophilus influenzae and Streptococcus pyogenes in tonsillar crypts and in mucosal site in the majority of cases, without evidence for ongoing viral infection. Immunohistochemical staining with the B-cell marker, L26, revealed that the follicles were significantly increased in size in TH as compared to RT.

The immune responses were studied in these disorders, focusing on cytokine and effector 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 from TH 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 found in the RT group compared to the TH group. We examined the presence of cytokines in cryopreserved 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 the RT group whereas IL-4 was upregulated in the TH group. We found that the cytokine producing cells were strictly compartmentalized with excessive IL-I and TGFB producing cells just beneath the surface and crypt epithelium. The immunoregulatory cytokines IL-2, IFNy, TNFB, G-CSF, GM-CSF, IL-4, 1L-5 and IL-IO were produced in the T-cell rich extrafollicular area. In order to assess the immunocapacity of the tonsil cells in the two clinical disorders, we used heat-inactivated Haemophilus influenzae and Streptococcus pyogenes to stimulate suspended tonsil cells in vitro. We found that both 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 between the two groups.

Severe clinical symptoms in acute infectious mononucleosis are linked to the development of extensive cellular immune activation. EBV-antigen positive cells were found in 17% of the B-cell population and co-localized to C D8+ T-cells in the extrafollicular area in IM. An increased incidence of IL-IB,IL-2, IFNy, IL-IO and IL-12 producing cells 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 in IM but not in RT, and localized to the extrafollicular site. Thus, the cytotoxic response seems to be crucial for control of acute EBV infection.

The localization of the immune response in tonsil tissue is visualized for the first time, illustrating the importance of the complexity of the local immune response mechanisms in different diseases. The increase of IL-4 may be one explanation for the enlarged follicles noticed in tonsillar hypertrophy.