IMMUNOHISTOCHEMICAL DETECTION OF CO-LOCALIZING CYTOKINE AND ANTIBODY-PRODUCING CELLS IN THE EXTRAFOLLICULAR AREA OF HUMAN PALATINE TONSILS

In vitro experiments have documented the role of cytokines in the regu lation of the human humoral immune response. Which cytokines are opera tive in vivo and in which lymphoid compartment interactions between cy tokine-producing T cells and antibody-forming B cells occur is still u nclear. For that reason we studied human tonsils using immunohistochem ical techniques. In tissue sections from tonsils in a resting stage af ter recurrent tonsillitis we observed cells producing IL-1alpha and tu mour necrosis factor-alpha (TNF-alpha) which were exclusively localize d in the mantle zone of the follicle and in the extrafollicular area. Furthermore, a high frequency of interferon-gamma (IFN-gamma)-producin g cells was detected in the extrafollicular area, but not inside the f ollicles. Occasional IL-2- and IL-4-producing cells were found in the extrafollicular area. Immunohistochemical detection of antibody isotyp es revealed that B cells, IgM-membrane-positive, were localized inside the follicles and mantle zones, whereas IgD-membrane-positive cells w ere mainly found in the mantle zones of secondary follicles. In contra st, plasma cells producing IgG1-4 and IgA1-2 were found in the extrafo llicular area. No IgD and IgE antibody-forming cells were detected in tonsils, whereas IgM antibody-forming cells were detected in the extra follicular area. The co-localization of cytokine-producing cells and a ntibody-forming cells in human tonsil suggests that T-B cell interacti ons, required for B cell differentiation and isotype switching, take p lace in the extrafollicular area.