Intraepithelial leukocytes of the intestinal mucosa in normal man and in Whipple's disease

Abstract

Intraepithelial lymphocytes (IEL) of the intestinal mucosa of normal man and of patients with Whipple's disease were studied by light microscopy of 1-micron-thick sections, and by electron microscopy of thin sections. IEL in normal human intestine tend to be elongated in outline, have few cytoplasmic organelles, have compact nuclei, and are unattached to epithelial cells. IEL in Whipple's disease are more likely to be activated in appearance, ie, to be larger and to contain more cytoplasmic organelles than IEL of normal intestine. The number of IEL/100 intestinal epithelial cells is similar in normal man and in patients with Whipple's disease. Other intraepithelial (IE) cells found in normal intestine include eosinophils and mast cells, and we note for the first time the presence of IE macrophages. There are no "globule leukocytes" in the intestine of normal man or of patients with Whipple's disease. Other IE cells found in the intestine in Whipple's disease include eosinophils, polymorphonuclear (PMN) leukocytes, and macrophages in untreated disease and intraepithelial macrophages in treated disease. These IE cells may be involved in the acute and chronic immune responses of the intestine.

Human intestinal intraepithelial lymphocytes.

“…Intraepithelial lymphocytes tend to be found largely at the base of epithelial cells, below epithelial nuclei.' I In the normal intestine these cells are largely medium sized (5)(6)(7)(8)(9) [tm in diameter), contain sparse cytoplasmic organelles including mitochondria, lysosomal granules, ribosomes (both isolated and polyribosomes), endoplasmic reticulum (rough predominating over smooth by a ratio of 2:1), and a small Golgi complex.5 The nucleus contains large amounts of heterochromatin and lesser amounts of euchromatin. Nucleoli are often present.…”

“…Clearly leucocytes other than lymphocytes are involved in the epithelial immune response in Whipple's disease.5 Curiously, there was a four-fold increase in number of intraepithelial lymphocytes in the single patient with Whipple's disease without intestinal involvement. 5 Intraepithelial lymphocytes have not been quantified in human graft-vshost disease but are clearly increased in murine graft-vs-host disease. 62 The intraepithelial lymphocytes count rose within 24 hours of induction of graft-vs-host disease while increases in crypt length occurred within three days.…”

The biology and pathobiology of the intestinal intraepithelial lymphocyte: A review of the literature

“…In addition some globule leucocytes and macrophages are present (16,50,60,63). Neutrophilic and eosinophilic granulocytes are rare in this compartment, but in inflammatory conditions of the digestive tract their numbers may be increased (3). Plasma cells are essentially located in the lamina propria.…”

“…In murine small intestine the mean number of IEL is 14-16/100 epithelial cells (23). In the human intestine the number is of the same order; in the normal jejunum it is about 20/100 epithelial cells (3). Probably due to the continuing digestion of the intraluminal mass resulting in a decreased antigenicity, the number of IEL/ 100 epithelial cells is lower in the distal parts of the digestive tract, resulting in a ratio of 13/100 in the normal ileum and a ratio of 5/100 in the normal colon (39).…”

“…These vessels, covered by a flat endothelium, were found to be situated at the base of the villi (32). Gut homing lymphocytes presumably leave the bloodstream through these vessels (3,38,52). Whereas B-cells localise in the lamina propria and proliferate and differentiate there, many T-cells penetrate the basal lamina and enter the epithelial layer.…”