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Prepublished online as a Blood First Edition Paper on September 26, 2002; DOI 10.1182/blood-2002-02-0475.
Submitted February 12, 2002
Accepted August 27, 2002
Functional expression of the eotaxin receptor CCR3 in CD30 positive cutaneous T-cell lymphoma
Martin Kleinhans, Adrian Tun-Kyi, Michel Gilliet, Marshall E Kadin, Reinhard Dummer, Guenter Burg, and Frank O Nestle*
Department of Dermatology, University of Zurich Medical School, Zurich, Switzerland; Department of Dermatology, J.W. Goethe-University Medical School, Frankfurt/Main, Germany
Department of Dermatology, University of Zurich Medical School, Zurich, Switzerland
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
* Corresponding author; email: nestle{at}derm.unizh.ch.
Little is known about mechanisms involved in skin specific homing of cutaneous T cell lymphoma (CTCL). Chemokine/chemokine receptor interactions have been implicated in homing of lymphoma cells to various tissue sites. We investigated tissue samples and tumor cell suspensions of patients with CD30 positive CTCL (n=8) and CD30 negative CTCL (Mycosis fungoides, n=6; Sezary Syndrome, n=6) for expression of the chemokine receptor CCR3, CCR4, CCR8 and the CCR3 ligands eotaxin/CCL11, MCP-3/CCL7 and RANTES/CCL5. Of 8 CD30 positive CTCL, 7 expressed CCR3, 4 CCR4 and none CCR8. CCR3 expression was not found in skin tissue samples from 12 CD30 negative CTCL. Co-expression of CCR3 and CD30 was demonstrated by flow cytometry in tumor cell suspensions. Internalization experiments demonstrated functionality of CCR3 expressed by freshly isolated tumor cells. Actin polymerization as well as migration in response to eotaxin was demonstrated in a CD30+ cutaneous lymphoma cell line. CCR3 ligand eotaxin/CCL11 was detected in lesional skin of CD30 positive CTCL by immunohistochemistry preferentially in tumor cells. Eotaxin/CCL11 expression in tumor cells was confirmed by intracellular immunofluorescence. Analysis of cytokine expression pattern of CCR3 bearing infiltrating cells showed a predominance of IL-4 but not IFN- protein expression consistent with a Th2 profile. These results suggest that expression of CCR3 and its ligand eotaxin/CCL11 play a role in the recruitment and retention of CD30 positive malignant T cells to the skin.
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