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

Abstract

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.

Keywords: CD15s; FoxP3; lichen planus; regulatory T cells.