Sensitization to epithelial antigens in chronic mucosal inflammatory disease. Characterization of human intestinal mucosa-derived mononuclear cells reactive with purified epithelial cell-associated components in vitro.

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Abstract

To explore the auto-reactive potential of cells infiltrating the gut mucosa in idiopathic chronic inflammatory bowel disease, intestinal lamina propria mononuclear cells (LPMC) were isolated, characterized morphologically and phenotypically, and evaluated for antigen-specific reactivity. The last was assessed by quantitating LPMC cytotoxic capabilities against purified, aqueous-soluble, organ-specific epithelial cell-associated components (ECAC) characterized previously. Enzyme-isolated inflammatory bowel disease LPMC were constituted primarily by T lymphocytes (57 +/- 12% OKT 3-positive), B lymphocytes (18 +/- 9% surface immunoglobulin-positive), and macrophages (11 +/- 6% esterase-positive), and were responsive to phytohemagglutinin (mean uptake 86,933 cpm/5 X 10(5) cells). LPMC present in abnormal segments from 71% of patients with chronic inflammatory bowel disease were cytotoxic for ECAC isolated from colon (12.5 +/- 8.9% specific lysis) and small bowel (7.1 +/- 6.5%), but not for kidney control antigen (0.8 +/- 1.1%) isolated in a manner analogous to that used for ECAC (P less than 0.02). In contrast, despite comparable responses to phytohemagglutinin (mean uptake 59,200 cpm/5 X 10(5) cells), LPMC from histologically normal mucosa of patients with benign (adult megacolon, Hirshsprung's disease, diverticulosis) or malignant disease failed to lyse indicator cells labeled with colon-derived ECAC (0.3 +/- 0.08%), small bowel-derived ECAC (0.4 +/- 1.11%), or kidney antigen (0.29 +/- 0.79%). LPMC reactivity for individual gel-purified macromolecules of small bowel-derived ECAC (designated as the "P" series of components) was greatest against component P1 (by 2-3-fold), but was detectable against three other purified components as well. The addition of patient's serum did not enhance cytotoxicity to ECAC. Characterization of the cytotoxic cell showed that it was nonadherent to plastic surfaces, bore T lymphocyte-specific markers detectable by OKT 11 and OKT 3 monoclonal antibodies, and could be depleted by removal of cells with receptors for sheep erythrocytes. ECAC-specific reactivity was markedly reduced (greater than 93%) in most experiments when LPMC were preincubated for 1 h with ECAC. These data support the concept that autosensitization to several epithelial cell-associated components has occurred in patients with chronic inflammatory bowel disease, and provide initial evidence that antigen-specific, cell-mediated mechanisms may play a role in the pathogenesis of these disorders.

Authors

J K Roche, C Fiocchi, K Youngman