The role of granzyme B-expressing CD8-positive T cells in apoptosis of keratinocytes in lichen planus

Abstract

Epidermal basal cell injury with colloid body formation is a characteristic feature of lichen planus. Infiltrated cells are thought to be responsible for the epidermal injury. Ultrastructural findings of colloid bodies are typical of apoptosis. Granzymes in cytotoxic T lymphocytes are involved in apoptosis probably together with perforin. Based on this background, we analyzed the role of granzyme B in the mechanisms of epidermal injury in lichen planus. On electron microscopy, basal and suprabasal cells showed condensed chromatin and fragmented nuclei which are typical morphological features of apoptosis. Nuclei of colloid bodies were positively stained by the in situ nick end labeling technique indicating that colloid bodies are subsequently formed in the process of apoptosis. Immunohistochemical staining showed CD8-positive infiltrating cells to contain granzyme B. Cells undergoing exocytosis also contained granzyme B. By immunoelectron microscopy, granzyme B molecules were observed to be secreted from a lymphocyte to an apoptotic keratinocyte. These findings suggest that granzyme B-positive CD8 cells seem to induce apoptosis of keratinocytes in lichen planus.

Intracellular versus extracellular granzyme B in immunity and disease: challenging the dogma

“…173,169 GrB-positive cells were found in close vicinity to apoptotic keratinocytes and through electron microscopy GrB was found to be transferred from a lymphocyte into an apoptotic keratinocyte, suggesting that GrB from lymphocytes is contributing to keratinocyte cell death in this disease. 168 GrB-expressing plasmacytoid DCs usually found in blood were seen in oral LP lesions and may contribute to GrB-associated damage in this disorder. 170 Stevens-Johnson syndrome and toxic epidermal necrolysis are rare and potentially life-threatening diseases involving keratinocyte apoptosis and epidermal necrosis, which are largely believed to be drug induced.…”

“…[161][162][163][164]166,168,173,176 GrB expression in most of these diseases was found to be localized to CTLs and GrB-specific disease implications were almost exclusively believed to be through intracellular CTLmediated apoptosis of keratinocytes and other resident cell types. As more cellular sources of GrB have been identified as of late and the emerging role of extracellular GrB activity gains traction, determining other GrB sources and examining the importance of extracellular GrB activity will be a necessity in dermatological research involving GrB.…”

The Pathogenesis of Oral Lichen Planus

“…Degenerating basal keratinocytes form colloid (Civatte, hyaline, cytoid) bodies that appear as homogenous eosinophilic globules. The ultrastructure of colloid bodies suggests that they are apoptotic keratinocytes, and recent studies using the end-labeling method demonstrated DNA fragmentation in these cells (Hashimoto, 1976;Weedon, 1980;Dekker et al, 1997;Shimizu et al, 1997;Bloor et al, 1999;Neppelberg et al, 2001). Epithelial basement membrane changes are common in OLP and include breaks, branches, and duplications (Jungell et al, 1989a;.…”

Oral lichen planus: Causes, diagnosis and management

“…The ultrastructure of colloid bodies suggests that they are apoptotic keratinocytes and recent studies using the end-labeling method demonstrated DNA fragmentation in these cells. [15][16][17][18] Epithelial basement membrane changes are common in OLP and comprise breaks, branches and duplications. 19 In addition, the basal keratinocyte anchoring elements (hemidesmosomes, filaments and fibrils) are disrupted.…”