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. 1981 Nov;44(3):489–497.

Cellular cytotoxicity and gastrointestinal inflammation in inbred rats: induction with gut organ-specific antigens

J K Roche, S R Cook, E D Day
PMCID: PMC1554942  PMID: 7319549

Abstract

Although the ability to induce with organ-specific antigens autoimmune inflammatory lesions in the brain and thyroid is well-established, it has not been accomplished for the gastrointestinal system. Therefore, purified rat intestinal glycoproteins (RGCG and RCG) with defined biochemical and immunological properties and known to be organ-specific, were employed to study immune responses in four highly inbred strains of rats. Animals subcutaneously immunized with RGCG/RCG (or saline in controls) and Mycobacterium butyricum as the primary adjuvant were followed weekly for (a) weight loss and diarrhoea; (b) development of specific antibody; (c) cell-mediated cytotoxicity by a 51Cr release assay; (d) pathological changes (graded I—IV) in intestine at the time of serial killing; and (e) increase in lamina propria cell count in histological sections taken from both macroscopically normal and abnormal bowel wall.

Disease incidence was highest in LOU/Mn strain rats injected with RCG, where small bowel lesions began at the fifth week after immunization (one of three animals), their frequency progressively increasing through the seventh week (four of five animals) when weight loss was most marked. Lewis strain rats injected with RCG had similar small bowel lesions at the sixth and seventh week. Colonic lesions were found in LOU/Mn strain rats injected with RGCG. Antibody-dependent cellular cytotoxic responses to RCG were detectable at both 50:1 and 10:1 effector to target ratios, occurred principally in injected animals who progressed to disease, and were correlated in time with the onset of lesions (weeks 5–7). Pathologically, all small bowel lesions were grade III (dark red granular mucosa) or IV (granular with obvious haemorrhage). Involved segments were 4–16 cm long, confined to the ileum, and diffuse without punctate ulcers. Colonic lesions were 2 cm long and diffusely hyperemic (grade II). Histologically, sections from diseased animals showed three changes: distortion (blunting) of villus shape, a hypercellular lamina propria (grade, moderate) and disruption of columnar epithelial lining cells. Two (ACI and Wistar—Furth) of the four strains studied were non-responders with respect to disease induction. We conclude that purified organ-specific gut glycoproteins can induce bowel wall pathological changes and antibody-dependent cellular cytotoxic reactions in susceptible strains of immunized rats. This technique may be useful for studying both the origin of, and the mediators for, autoimmune disease of the intestine.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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