title: Concomitant in vivo production of 19 different cytokines in human tonsils.
abstract: Accumulating data indicate that cytokines, peptides involved in regulation of both physiological and pathological immune responses, are produced predominantly at the site of local antigen stimulation. Cytokine-producing cells were detected at the protein level in human tonsil tissue obtained from children with recurrent tonsillitis or infectious mononucleosis (IM). Concomitant production of 19 different human cytokines, interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-1 receptor antagonist (ra), IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, tumour necrosis factor-alpha (TNF-alpha), TNF-beta, interferon-gamma (IFN-gamma) and transforming growth factor-beta 1-3 (TGF-beta 1-3), was identified at a single-cell level by indirect immunohistochemical staining procedures and use of carefully selected cytokine-specific antibodies (Ab). Fresh frozen sections were fixed with 4% paraformaldehyde and permeabilized by 0.1% saponin treatment, eluting cholesterol from the cell-surface membrane and the Golgi complex. The intracellular localization of all cytokines, except IL-1 and IL-1ra, was demonstrated by a characteristic local cytoplasmic perinuclear configuration in producer cells. In addition, the immunoreactivity for certain cytokines (IL-2, IL-4, IL-5, G-CSF and GM-CSF) was expressed on the cell membranes and extended over a large extracellular area encompassing the producer cell. Localization of the cytokine to the Golgi organelle was established by co-staining with a monoclonal antibody (mAb) specific to the Golgi complex. Both the extra- and intracellular cytokine staining reactions could be blocked by preincubation of the cytokine-specific Ab with the corresponding purified natural or recombinant cytokine. A complex cytokine pattern was established in both groups studied, where most T-helper type 1 (Th1) and Th2 lymphokines were expressed in the tonsils but at different frequencies and localizations. Cells expressing IL-4, IL-5, IL-10 and IL-13, (Th2 response) were evident at higher frequencies in recurrent tonsillitis compared to sections from IM, which were associated with a more pronounced IL-2, IFN-gamma and TNF-beta expression.
authors: Department of Immunology, Arrhenius Laboratories for Natural Sciences, Stockholm University, Sweden.
authors: J
authors: J
authors: Andersson
authors: J
authors: J
authors: Abrams
authors: L
authors: L
authors: Björk
authors: K
authors: K
authors: Funa
authors: M
authors: M
authors: Litton
authors: K
authors: K
authors: Agren
authors: U
authors: U
authors: Andersson
mesh_terms: D000208:Acute Disease; D002648:Child; D003115:Colony-Stimulating Factors / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D007124:Immunoenzyme Techniques; D007244:Infectious Mononucleosis / Q000276:immunology*; D007378:Interleukins / Q000096:biosynthesis; D008222:Lymphokines / Q000096:biosynthesis; D014066:Palatine Tonsil / Q000276:immunology*; D012008:Recurrence; D014069:Tonsillitis / Q000276:immunology*
chemical_list: D003115:Colony-Stimulating Factors; D016207:Cytokines; D007378:Interleukins; D008222:Lymphokines