Skip to main content


Log in

The role of perforin-mediated apoptosis in lichen planus lesions

  • Original Paper
  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript


Lichen planus is recognized as a T-cell-mediated disease. Histologically, it is characterized by the formation of colloid bodies representing apoptotic keratinocytes. The apoptotic process mediated by CD8+ cytotoxic T lymphocytes (CTLs) and NK cells mainly involves two distinct pathways: the perforin/granzyme pathway and the Fas/FasL pathway. So far, little is known regarding the role of perforin-mediated apoptosis in lichen planus. In the present study, the expression and distribution of perforin, T and NK cell subsets in the epidermis and dermis of lesional and nonlesional lichen planus skin were studied. Skin biopsy specimens from lesional and nonlesional skin of ten patients with lichen planus and eight healthy persons were analysed by immunohistochemistry. Significant accumulation of T cells, particularly of CD4+ and CD8+ subsets, was found in both epidermis and dermis of lichen planus lesions compared with nonlesional and healthy skin. There were no significant differences in the incidence of NK cells (CD16+ and CD56+) between lesional, nonlesional and healthy skin. Perforin expression was significantly upregulated in the epidermis of lichen planus lesions. In conclusion, accumulation of perforin+ cells in the epidermis of lichen planus lesions suggest a potential role of perforin in the apoptosis of basal keratinocytes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3a–c

Similar content being viewed by others


  1. Agarwal R, Saraswat A (2002) Oral lichen planus: an update. Drugs Today (Barc) 38:533–547

    Google Scholar 

  2. Sugerman PB, Savage NW, Walsh LJ, Zhao ZZ, Zhou XJ, Khan A, Seymour GJ, Bigby M (2002) The pathogenesis of oral lichen planus. Crit Rev Oral Biol Med 13:350–365

    CAS  PubMed  Google Scholar 

  3. Walsh LJ, Savage NW, Ishi T, Seymour GJ (1990) Immunopathogenesis of oral lichen planus. J Oral Pathol Med 19:389–396

    CAS  PubMed  Google Scholar 

  4. Khan A, Farah CS, Savage NW, Walsh LJ, Harbrow DJ, Sugerman PB (2003) Th1 cytokines in oral lichen planus. J Oral Pathol Med 32:77–83

    Article  CAS  PubMed  Google Scholar 

  5. Thornhill MH (2001) Immune mechanisms in oral lichen planus. Acta Odontol Scand 59:174–177

    Article  CAS  PubMed  Google Scholar 

  6. Teraki Y, Shiohara T (1999) Apoptosis and the skin. Eur J Dermatol 9:413–426

    CAS  PubMed  Google Scholar 

  7. Podack ER (1995) Functional significance of two cytolytic pathways of cytotoxic T lymphocytes. J Leukoc Biol 57:548–552

    CAS  PubMed  Google Scholar 

  8. Griffiths GM, Mueller C (1991) Expression of perforin and granzymes in vivo: potential diagnostic markers for activated cytotoxic cells. Immunol Today 12:415–419

    Article  CAS  PubMed  Google Scholar 

  9. Yagita H, Nakata M, Kawasaki A, Shinkai J, Okumura K (1992) Role of perforin in lymphocytes-mediated cytolysis. Adv Immunol 51:215–241

    CAS  PubMed  Google Scholar 

  10. Shimizu M, Higaki J, Higaki M, Kawashima M (1997) The role of granzyme B-expressing CD8-positive T cells in apoptosis of keratinocytes in lichen planus. Arch Dermatol Res 289:527–532

    Article  CAS  PubMed  Google Scholar 

  11. Walton LJ, Macey MG, Thornhill MH, Farthing PM (1998) Intra-epithelial subpopulations of T lymphocytes and Langerhans cells in oral lichen planus. J Oral Pathol Med 27:116–123

    CAS  PubMed  Google Scholar 

  12. Akasu R, From L, Kahn HJ (1993) Lymphocyte and macrophage subsets in active and inactive lesions of lichen planus. Am J Dermatopathol 15:217–223

    CAS  PubMed  Google Scholar 

  13. Villarroel Dorrego M, Correnti M, Delgado R, Tapia FJ (2002) Oral lichen planus: immunohistology of mucosal lesions. J Oral Pathol Med 31:410–414

    Article  PubMed  Google Scholar 

  14. De Panfilis G, Manara GC, Ferrari C, Torresani C (1988) Simultaneous colloidal gold immunoelectronmicroscopy labelling of CD1a, HLA-DR and CD4 surface antigens of human epidermal Langerhans cells. J Invest Dermatol 91:547–552

    Article  PubMed  Google Scholar 

  15. Zhou XJ, Sugerman PB, Savage NW, Walsh LJ, Seymour GJ (2002) Intra-epithelial CD8+ T cells and basement membrane disruption in oral lichen planus. J Oral Pathol Med 31:23–27

    CAS  PubMed  Google Scholar 

  16. Iijima W, Ohtani H, Nakayama T, Sugawara Y, Sato E, Nagura H, Yoshie O, Sasano T (2003) Infiltrating CD8+ T cells in oral lichen planus predominantly express CCR5 and CXCR3 and carry respective chemokine ligands RANTES/CCL5 and IP-10/CXCL10 in their cytolytic granules: a potential self-recruiting mechanism. Am J Pathol 163:261–268

    CAS  PubMed  Google Scholar 

  17. Shiohara T, Moriya N, Nagashima M (1988) The lichenoid tissue reaction: a new concept of pathogenesis. Int J Dermatol 27:365–374

    CAS  PubMed  Google Scholar 

  18. Podack ER (1992) Perforin: structure, function and regulation. Curr Topics Microbiol Immunol 178:175–184

    CAS  Google Scholar 

  19. Rubesa G, Podack ER, Sepcic J, Rukavina D (1997) Increased perforin expression in multiple sclerosis patients during exacerbation of disease in peripheral blood lymphocytes. J Neuroimmunol 74:198–204

    Article  CAS  PubMed  Google Scholar 

  20. Gulan G, Ravlic-Gulan J, Strbo N, Sotosek V, Nemec B, Matovinovic D (2003) Systemic and local expression of perforin in lymphocyte subsets in acute and chronic rheumatoid arthritis. J Rheumatol 30:660–670

    CAS  PubMed  Google Scholar 

  21. Griffiths GM, Alpert S, Lambert E, McGuire J, Weissman IL (1992) Perforin and granzyme A expression identifying cytolytic lymphocytes in rheumatoid arthritis. Proc Natl Acad Sci U S A 89:549–553

    CAS  PubMed  Google Scholar 

  22. Yasukawa M, Ohminami H, Arai J, Kasahara Y, Ishida Y, Fujita S (2000) Granule exocytosis and not the fas/fas ligand system, is the main pathway of cytotoxicity mediated by alloantigen-specific CD4(+) as well as CD8(+) cytotoxic T lymphocytes in humans. Blood 95:2352–2355

    CAS  PubMed  Google Scholar 

  23. Schnyder B, Frutig K, Yawalkar N, Limat A, Pichler WJ (1998) T cell cytotoxicity in sulfamethoxazole induced skin reaction. Clin Exp Allergy 28:1412–1417

    Article  CAS  PubMed  Google Scholar 

  24. Sugerman PB, Savage NW, Seymour GJ, Walsh LJ (1996) Is there a role of tumor necrosis factor-alpha (TNF-α) in oral lichen planus? J Oral Pathol Med 25:219–224

    CAS  PubMed  Google Scholar 

Download references


These investigations are financially supported by the Ministry of Science and Technology of the Republic of Croatia.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Marija Kaštelan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kaštelan, M., Prpić Massari, L., Gruber, F. et al. The role of perforin-mediated apoptosis in lichen planus lesions. Arch Dermatol Res 296, 226–230 (2004).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: