Immunoelectron microscopic localization of HLA-DR antigen in control small intestine and colon and in inflammatory bowel disease

Abstract

We have elucidated the distribution of I2 (HLA-DR) antigen in control and inflammatory bowel disease specimens, using immunoelectron microscopic methods. Control small intestinal epithelium and inflammatory bowel disease epithelium expressed 12 antigen, while control colonic epithelium did not. I2 expression by enterocytes was more frequent on the lateral and basal surface than on the microvillus surface. Two of three M cells in control ileum expressed I2 antigen. I2-positive intraepithelial lymphocytes were rarely detected in both control and disease specimens. I2-positive lamina propria lymphocytes were significantly increased in inflammatory bowel disease, while I2-positive lamina propria lymphocytes were virtually absent in control specimens. I2-positive mononuclear cells in the intestinal lamina propria were largely macrophages and monocytes in both control and inflammatory bowel disease specimens. I2-positive mononuclear cells resembling dendritic cells were not detected in control or disease specimens. Furthermore, there were no significant morphological differences in I2-positive or -negative macrophages and monocytes in control and disease specimens. The expression of I2 antigen on Schwann cells was detected more frequently in disease specimens than in control specimens. Capillary endothelia of both control and disease specimens expressed I2 antigen. We demonstrate that I2 expression is present on surface membranes of both immune and nonimmune cells of the intestine and colon and show that this expression is more prominent in inflammatory bowel disease than in control intestine and colon. Further studies are required to determine whether this finding is meaningful in terms of antigen presentation and whether this apparent "immune activation" is involved in the pathogenesis of inflammatory bowel disease.

Vectorial function of major histocompatibility complex class II in a human intestinal cell line

“…A first striking feature observed was the polarized nature of class II HLA‐DR expression, with surface expression almost entirely restricted to the basolateral surface. This distribution is consistent with the site of T‐cell/epithelial cell interaction in vivo , and has been reported in some electron microscope studies of HLA distribution, 28 , 29 as well as in a recent study on T84 cells 9 . However, other studies using light immunohistochemistry have reported HLA‐DR on both surfaces of the intestinal epithelium, and this question clearly needs further study to resolve these apparent contradictions.…”

Glial cells in the gut

“…How is the inflammatory process in disorders like CD–which presumably originate in the mucosa 128 –directed to the ENS? A number of findings indicate that enteric glia may be instrumental to attract immune cells: lymphocytic infiltrates in the ENS of CD patients are associated with glial major histocompatibility complex (MHC) class II expression, 129–131 and ultrastructural studies have revealed close contacts between CD45RO + T‐cells and MHC II‐expressing glial cells in the ENS of these patients, 131 strongly suggesting functional glia–lymphocyte interactions. Regularly, glial MHC II expression and lymphocytic infiltration of the ENS were accompanied by signs of neuronal damage 131 …”

Role of enteric glial cells in inflammatory bowel disease

“…EGCs share this antigen-presenting capability as demonstrated in (GFAP-HA ϫ HA-TCR)F1 double transgenic mice. Surface MHC class II molecules are profoundly upregulated during Crohn's disease (Hirata et al, 1986;Geboes et al, 1992). Axonal abnormality and necrosis of enteric neurons (Dvorak and Silen, 1985) are strongly predictive of disease recurrence in noninflamed Crohn's disease tissues and are often associated with T-cell infiltration of neuronal plexi in a fashion that may be modeled using (GFAP-HA ϫ HA-TCR)F1 double transgenic mice (D'Haens et al, 1998;Geboes and Collins, 1998).…”