Modulation of intestinal immune reactivity by interleukin 2. Phenotypic and functional analysis of lymphokine-activated killer cells from human intestinal mucosa.
There is evidence indicating that interleukin 2 may be important in the regulation of intestinal immunity, as suggested by its capacity to induce nonspecific cytotoxic (lymphokine-activated killer) activity from human intestinal mucosal mononuclear cells. The present study was designed to further explore the phenotypic and functional changes induced by interleukin 2 on intestinal lymphocytes derived from inflammatory bowel disease and control tissues. Immunohistology of intestinal mucosa demonstrated few cells bearing the activation antigen recognized by anti-Tac (anti-interleukin 2 receptor) monoclonal antibody. However, when isolated lamina proprial mononuclear cells were exposed to interleukin 2 in culture, the number of Tac-positive cells increased dramatically, a phenomenon paralleled by the generation of lymphokine-activated killer cell activity. This cytotoxic function was critically dependent on the continuous availability of interleukin 2, but not on the expression of the Tac antigen, since Tac-negative cells were also cytotoxic. Depletion of natural killer cells, fractionation into T cell-enriched and -depleted cells before and after culturing with interleukin 2, and separation into Tac-positive and -negative cells after interleukin 2 activation failed to eliminate lymphokine-activated killer cell activity, suggesting that this phenomenon is mediated by phenotypically and functionally heterogeneous cell subsets. During the induction of lymphokine-activated killer cells variable amounts of interferon-gamma were produced, but these did not correlate with the degree of cytotoxicity. No differences were observed between the response to interleukin 2 by inflammatory bowel disease and control cells. Therefore, in view of its capacity to induce significant phenotypic and functional changes in different subpopulations of intestinal mucosal mononuclear cells, interleukin 2 should be regarded as an important modulator of intestinal immune reactivity.
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D003424:Crohn Disease / Q000276:immunology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010641:Phenotype
D000276:Adjuvants, Immunologic; D007376:Interleukin-2; D007371:Interferon-gamma