Phenotypically non‐suppressive cells predominate among FoxP3‐positive cells in oral lichen planus

Background Oral lichen planus ( OLP ) is a common T‐cell‐dominated oral chronic inflammatory disease occurring in periods of remission, quiescence, activity with pronounced inflammation, and acute ulceration. Cell infiltrates in OLP contain varying numbers of CD4 + T cells expressing the transcription factor FoxP3. FoxP3 + CD4 + T cells are, however, a heterogeneous cell population containing suppressive and non‐suppressive cells, and their distribution in infiltrates from OLP is unknown. Methods Biopsies were taken from normal oral mucosa ( n = 8) and OLP lesions ( n = 19), and a set of in situ methods for the determination of the functional phenotype of FoxP3 + CD4 + T cells was applied. Results Numbers of FoxP3 + CD4 + T cells were highest in the atrophic form of the disease, yet low in the ulcerative form. The main FoxP3 + CD4 + T‐cell population observed was FoxP3 + CD45RA − CD25 + CD45RO + and CD15s − , a phenotype delineating a non‐suppressive subset. Numbers of cells with an actively suppressing phenotype (FoxP3 + CD45RA − CD25 + CD45RO + and CD15s + ) were, however, about twice as high in reticular lesions as compared with the atrophic form. Many FoxP3 + CD4 + T cells expressed T‐bet, the hallmark transcription factor for IFN ‐γ‐producing T cells, indicating that they may enhance immune and inflammatory responses rather than suppress them. Conclusions The absence of actively suppressing FoxP3 + CD4 + T cells may in part explain why OLP is a remarkably persisting condition, in spite of the presence of substantially high numbers of FoxP3 + CD4 + T cells. The findings emphasize that it is crucial to examine not only numbers but also functional phenotype of FoxP3 + CD4 + T cells in human tissues.