title: The role of cytotoxic skin-homing CD8+ lymphocytes in cutaneous cytotoxic T-cell lymphoma and pityriasis lichenoides.
abstract: BACKGROUND
  Pityriasis lichenoides (PL) is a rare cutaneous lymphoproliferative disorder of unknown origin. Malignant transitions of PL have been described, but are very rare. We recently observed the fatal course of a 26-year-old patient who presented with a clinical picture resembling PL but had cytotoxic CD8+ T-cell lymphoma of the skin (CxCTL). This case prompted us to reinvestigate the role of cytotoxic T lymphocytes in PL and its relationship to antiviral immunity.
  
  
  METHODS
  Skin biopsy specimens of 11 patients with PL and two biopsy specimens of CxCTL were included. In all, 5 biopsy specimens taken from healthy skin and 5 samples of varicella-zoster virus (VZV) skin lesions were analyzed for control purposes. The inflammatory infiltrate was characterized by immunohistochemistry using monoclonal antibodies against CD3, CD4, CD8, CD20, cutaneous lymphocyte-associated antigen (CLA), CCR4, CXCR3, Granzyme B, Tia-1, and MxA. Flow cytometry was used to analyze the expression of chemokine receptors on peripheral blood mononuclear cells in CxCTL.
  
  
  RESULTS
  The CxCTL skin lesions were dominated by a dense infiltration of CD8+ cytotoxic lymphocytes with a skin-homing CLA+ CCR4+ phenotype. PL and VZV skin lesions were also characterized by a predominantly CD8+ T cellular infiltrate with strong expression of the cytotoxic molecules Granzyme B and Tia-1 and the skin-homing molecules CLA and CCR4. Coexpression analyses confirmed that skin CLA+ CD8+ cytotoxic T cells are present in CxCTL, VZV, and PL skin lesions. Strong lesional production of the antiviral protein MxA, which is specifically induced by type I interferons, could be found in all investigated disorders. The study was based on histologic, immunohistologic, and flow cytometric analyses in a limited number of patients, because of the rareness of the investigated diseases.
  
  
  CONCLUSIONS
  Our results revealed a striking similarity between the immunohistologic picture of malignant CxCTL, benign PL, and VZV skin lesions. Strong expression of the antiviral protein MxA in all disorders supports the view that a common antiviral immune response pattern leads to aberrant skin recruitment of CLA+ CCR4+ cytotoxic T lymphocytes in PL and CxCTL.
authors.affiliation: Department of Dermatology, Institute of Pathology, University of Bonn, Bonn, Germany. joerg.wenzel@ukb.uni-bonn.de
authors.forename: Joerg
authors.initials: J
authors.lastname: Wenzel
authors.forename: Ines
authors.initials: I
authors.lastname: Gütgemann
authors.forename: Moritz
authors.initials: M
authors.lastname: Distelmaier
authors.forename: Manfred
authors.initials: M
authors.lastname: Uerlich
authors.forename: Sandra
authors.initials: S
authors.lastname: Mikus
authors.forename: Thomas
authors.initials: T
authors.lastname: Bieber
authors.forename: Thomas
authors.initials: T
authors.lastname: Tüting
mesh_terms: D000328:Adult; D017809:Fatal Outcome; D005434:Flow Cytometry; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016410:Lymphoma, T-Cell, Cutaneous / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D064547:Myxovirus Resistance Proteins; D017514:Pityriasis Lichenoides / Q000276:immunology / Q000503:physiopathology*; D016201:Receptors, Lymphocyte Homing / Q000276:immunology / Q000502:physiology*; D012878:Skin Neoplasms / Q000276:immunology / Q000503:physiopathology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000502:physiology*
chemical_list: C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D016201:Receptors, Lymphocyte Homing; D019204:GTP-Binding Proteins