Intraepithelial CD8+ lymphocytes as a predictive diagnostic biomarker for the remission of oral lichen planus.

Oral lichen planus (OLP) is an autoimmune inflammatory disease of the oral mucosa whose etiology remains unknown. Moreover, the possibility of OLP being a premalignant change is under debate. Various types of immune cells infiltrate the OLP lesion and affect its clinicopathological features. However, the diversity of infiltrating immune cells has not been fully clarified in relation to OLP diagnosis. In this study, we quantitatively examined CD8+ lymphocyte infiltration by immunohistochemistry, which is the principal effector of cytotoxic immune reaction in 123 cases of OLP specimens. Our examination revealed that high-grade intraepithelial CD8+ lymphocyte infiltration was associated with a high remission rate. Evaluation of the infiltration of T-bet+ and FoxP3+ lymphocytes, which corresponded to the Th1 and Treg CD4+ subsets, respectively, showed that intraepithelial CD8+ lymphocytes were associated with the remission rate in the subgroup with a higher T-bet/FoxP3 subset balance that is inducible for cytotoxic immunity. We also investigated the cutoff value of CD8+ lymphocyte infiltration for histopathological diagnosis. By microscopic counting, 16 cells/high-power field, which was also confirmed in the validation cohort, was established as the cutoff value for intraepithelial CD8+ lymphocyte infiltration for predicting the remission of OLP. Remitting OLP might be different from refractory OLP in terms of etiology and clinical behavior. Thus, intraepithelial CD8+ lymphocytes may serve not only as a predictive biomarker for remission but also as an area for further biomedical research regarding the etiology and premalignant potential of OLP.