The production of immunoregulatory cytokines is localized to the extrafollicular area of human tonsils.

The localization and production at the single cell level of 19 different human cytokines, IL-1 alpha, IL-1 beta, IL-1ra, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, TNF alpha, TNF beta, IFN gamma, GM-CSF, G-CSF, and TGF beta 1-3, were studied in cryopreserved tonsillar tissue using immunohistochemical staining. The cytokine producing cells, with the exception of IL-1 expressing cells, had a characteristic morphology due to the accumulation of cytokine onto the Golgi organelle. The production of each cytokine was localized to specific compartments in tonsillar tissue sections from children with tonsillar hypertrophy or recurrent tonsillitis in the resting state. Immunoregulatory cytokines such as IL-2, IL-3, IL-4, G-CSF, GM-CSF and TGF beta were produced in the extrafollicular area and entrapped on the cell membranes as well as in pudels in the extracellular matrix surrounding the producer cells. The dominating cytokines both in tissues from recurrent tonsillitis and tonsillar hypertrophy were GM-CSF, G-CSF, and TGF beta 1-3 which were synthezised predominantly in the reticular crypt site. IL-1 alpha, beta and IL-1ra, on the other hand, were localized to the surface and crypt epithelium and to scattered regions in the extrafollicular area. IL-2, IL-6, IFN gamma and IL-10 were found much more often in sections obtained from recurrent tonsillitis tissue compared with those from tonsillar hypertrophy. Reversely, an excessive production of IL-4 was noted in tonsillar hypertrophy compared with that in recurrent tonsillitis. Thus, concomitant production of multiple cytokines was evident with similarities but also differences in cytokine pattern between the two groups studied. The data suggest that T-cell mediated B-cell activation and differentiation take place in the extrafollicular area. Children with recurrent tonsillitis had a higher amount of B-cells and monocytes compared with children with tonsillar hypertrophy. However, the number of CD3, CD4, CD8 or cytoplasmic Ig-positive cells did not differ between the two groups.