A. Nakazawa et al., Functional expression of costimulatory molecule CD88 on epithelial cells in the inflamed colonic mucose, GASTROENTY, 117(3), 1999, pp. 536-545
Background & Aims: Costimulatory signals are essential for T-cell activatio
n. The aim of this study was to demonstrate expression of costimulatory mol
ecules CD86 and CD80 in human colonic epithelial cells and assess their fun
ctional roles in the activation of T cells in inflamed colonic mucosa. Meth
ods: CD86 and CD80 expression was assessed by immunohistochemistry of colon
ic mucosa, reverse-transcriptionpolymerase chain reaction, and flow cytomet
ric analysis of isolated colonic epithelial cells and cell lines. Costimula
tory effect of CD86-expressing colonic epithelial cells on purified CD4(+)
T-cell proliferation was also assessed at suboptimal phytohemagglutinin sti
mulation. Results. CD86 and CD80 messenger RNA was detected in isolated col
onic epithelial cells from normal and inflamed mucosa of patients with ulce
rative colitis. Immunohistochemistry and flow cytometric analysis of coloni
c epithelial cells confirmed cell surface expression of CD86 protein in inf
lamed colonic mucosa. Cell surface expression of CD86 protein was increased
in the colonic epithelial cell line HT29-18-N2 after interferon gamma stim
ulation. Purified CD4(+) T cells proliferated in response to suboptimal phy
tohemagglutinin costimulated with interferon gamma-stimulated HT29-18-N2, a
nd these proliferative responses were efficiently inhibited by the addition
of anti-CD86 monoclonal antibody. Costimulatory effect of CD86-expressing
colonic epithelial cells isolated from inflamed mucosa of ulcerative coliti
s was also demonstrated at suboptimal phytohemagglutinin stimulation in CD4
(+) T cells. Conclusions: Colonic epithelial cells may act as antigen-prese
nting cells, and contribute to the activation off cells through costimulato
ry molecule CD86 expression in inflamed colonic mucosa.