CD8+ T residual memory cells in Lichen planus

Clinical significance of CD8+ tissue-resident memory (TRM) T cells in lichen planus (LP):

CD8+ TRM cells form a localized reservoir of chronic inflammation in lichen planus lesions, capable of rapid and repeated activation at sites of previous inflammation, thereby contributing to disease persistence and flare-ups. These cells recognize antigens presented on keratinocytes via MHC class I molecules and mediate cytotoxic effects primarily through granule exocytosis, releasing perforin, granzyme B, and granulysin, which induce keratinocyte apoptosis and characteristic epidermal damage seen in LP lesions. Their cytotoxic activity is a critical mechanism underpinning basal keratinocyte injury and the subsequent clinical manifestations of LP. Moreover, CD8+ TRM cells interact with CD4+ T helper cells and other immune components, amplifying the local immune response through the production of pro-inflammatory cytokines such as IFN-γ and TNF-α, which further perpetuate inflammation and tissue damage.

Functionally, these TRM cells are sustained within the lesional skin by signals including chemokines like CXCL9 and CXCL10 and cytokines such as IL-15, supporting their maintenance and survival in situ. The persistent presence of CD8+ TRM cells explains the chronic and relapsing nature of LP despite systemic immunosuppressive therapies, as these cells reside locally and can evade systemic immune modulation. Their strategic epidermotropic localization, especially near the basement membrane zone, facilitates continuous recognition and destruction of keratinocytes presenting altered or exogenous antigens, thereby driving the clinical and histopathological pattern of LP.

From a clinical perspective, the density of CD8+ TRM cells in LP lesions correlates with disease activity and severity, as evidenced by immunohistochemical studies showing increased CD8+ T cell infiltration at lesional sites. Their presence may also influence therapeutic responses, with potential implications for targeted treatments aimed at modulating TRM cell survival or function to achieve lasting remission. The interaction of these cells with other inflammatory axes, including Th1 and IL-23/Th17 pathways, underscores their central role within the complex immunopathogenic network of LP.

In summary, CD8+ tissue-resident memory T cells are key effectors in the immunopathogenesis of lichen planus, perpetuating localized cytotoxicity and chronic inflammation, thereby linking immunological mechanisms to clinical disease persistence and recurrence. Targeting these cells or their microenvironment may represent a promising therapeutic strategy to control refractory or recurrent forms of LP.