The existence of CD4(+) T lymphocytes with cytotoxic activity in minor sali
vary gland (MSG) biopsies from Sjogren's syndrome (SS) patients was investi
gated using in situ double immunohistochemistry technique. The presence of
dendritic cells (DC) in SS lesions was examined by using single and double
immunohistochemistry methods and a panel of different MoAbs to specific cel
l surface markers (i.e. CD3, CD11c, DRC). Furthermore, the ultrastructural
morphology of DC was characterized by electron microscopy (EM). Immunogold
labelling technique using the DRC surface marker was also applied. Finally,
we investigated the existence of germinal centres (GC) in the salivary gla
nd lesions of SS patients. Seven patients with primary SS and five patients
with non-specific sialadenitis were the subjects of this study. Our result
s indicate the existence of a CD4(+) cytotoxic cell population that utilize
s perforin-mediated cell destructions as they expressed perforin mRNA. Quan
titative analysis of these cells revealed that they comprised approximately
20% of the existing T lymphocytes. We also identified a population of CD4(
+) T cells that expressed the CD11c activation marker. Furthermore, we obse
rved a distinct cell subtype which expressed the DRC cell surface marker. T
hese cells had the characteristic ultrastructural morphology of DC and were
DRC+ when examined by immunoelectron microscopy. Finally, the formation of
GC structures in the histopathologic lesions of the salivary glands was ob
served. The above findings indicate that both CD4(+) cytotoxic T lymphocyte
s (CTL) and DC may be involved in the initiation and perpetuation of SS pat
hogenesis. Moreover, the formation of GC in the lesions reveals a possible
mechanism for insiru differentiation and proliferation of activated B lymph
ocytes.