The role of cytotoxic skin-homing CD8+ lymphocytes in cutaneous cytotoxic T-cell lymphoma and pityriasis lichenoides - 21/08/11
Bonn, Germany
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.
Conclusion |
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.
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Funding source: Deutsche Forschungsgemeinschaft (FOR 367/2 TP7) and Deutsche Krebshilfe (for I.G.). Conflicts of interest: None identified. |
Vol 53 - N° 3
P. 422-427 - septembre 2005 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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