Oral submucous fibrosis (OSF) is a chronic disease of the oral cavity
characterized by inflammation and progressive mucosal fibrosis. These
reactions may be the result of either direct stimulation from exogenou
s antigens like areca alkaloids or by changes in tissue antigenicity t
hat may lead to an autoimmune response. This study investigated the pr
esence and distribution of inflammatory cells and MHC class II antigen
expression by epithelial and immunocompetent cells using a three-stag
e immunoperoxidase method on frozen sections. Thirty OSF tissue specim
ens and ten normal buccal mucosae were studied and compared. All tissu
es were investigated using antibodies to T cells (CD3), T helper/induc
er cells (CD4), T suppressor/cytotoxic cells (CDS), B cells (CD20), na
ive T cells and monocytes (CD45RA), macrophages, Langerhans' cells (CD
68) and HLA-DR-positive cells (HLA-DR alpha). The predominant cell pop
ulations detect and HLA-DR-positive cells. The distribution of CD4-pos
itive cells was similar to that of CD3-positive cells, which were scat
tered, often uniformly distributed, both in the epithelium and connect
ive tissue. CD8-positive cells were occasionally seen in the normal ep
ithelium and lamina propria. Few scattered B cells (CD20) and macropha
ges (CD68) were observed in normal mucosa. Naive T cells (CD45RA) were
seen in all normal tissues focally concentrated around the connective
tissue papillae, with a similar distribution to that of CD3-positive
cells. All normal sections showed HLA-DR-positive cells scattered both
in the epithelium and in the lamina propria. Epithelial cells did not
show any positive reaction to this antibody and many intraepithelial
positive cells showed a dendritic morphology. The cell populations det
ected in OSF showed higher numbers of CD3 and HLA-DR-positive cells co
mpared with those of the normal tissues. The pattern of staining for C
D4-positive cells in OSF tissues was similar to that of CD3-positive c
ells both in the epithelium and connective tissue and was higher than
that in normal tissues. A few scattered CD8-positive cells and only oc
casional CD20- and CD68-positive cells were seen in OSF sections. Few
CD45RA-positive cells were found in the epithelium and lamina propria
of OSF sections. However, OSF specimens showed high numbers of HLA-DR-
positive cells in the basal layer of the epithelium, juxtaepithelium a
nd in the lamina propria in a similar distribution to that of CD3 cell
s compared with the normal tissues. Most HLA-DR-positive cells in the
epithelium showed dendrites directed vertically towards the surface. T
he increased evidence of CD4 and HLA-DR-positive cells in OSF tissues
suggests that most lymphocytes were activated and shows an increased p
resence of Langerhans' cells. The presence of these immunocompe tent c
ells and high ratio of CD4 to CD8 in OSF tissues suggest an ongoing ce
llular immune response leading to a possible imbalance of immunoregula
tion and alteration in local tissue architecture.