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In vitro experiments have documented the role of cytokines in the regulation of the human humoral immune response. Which cytokines are operative in vivo and in which lymphoid compartment interactions between cytokine-producing T cells and antibody-forming B cells occur is still unclear. For that reason we studied human tonsils using immunohistochemical techniques. In tissue sections from tonsils in a resting stage after recurrent tonsillitis we observed cells producing IL-1 alpha and tumour necrosis factor-alpha (TNF-alpha) which were exclusively localized in the mantle zone of the follicle and in the extrafollicular area. Furthermore, a high frequency of interferon-gamma (IFN-gamma)-producing cells was detected in the extrafollicular area, but not inside the follicles. Occasional IL-2- and IL-4-producing cells were found in the extrafollicular area. Immunohistochemical detection of antibody isotypes revealed that B cells, IgM-membrane-positive, were localized inside the follicles and mantle zones, whereas IgD-membrane-positive cells were mainly found in the mantle zones of secondary follicles. In contrast, plasma cells producing IgG1-4 and IgA1-2 were found in the extrafollicular area. No IgD and IgE antibody-forming cells were detected in tonsils, whereas IgM antibody-forming cells were detected in the extrafollicular area. The co-localization of cytokine-producing cells and antibody-forming cells in human tonsil suggests that T-B cell interactions, required for B cell differentiation and isotype switching, take place in the extrafollicular area.