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Immune Function Abnormalities in Peripheral Blood Mononuclear Cell Cytokine Expression Differentiates Stages of Cutaneous T-Cell Lymphoma/Mycosis Fungoides

Authors' Affiliations: Department of Dermatology, Henry Ford Hospital, Detroit, Michigan

Requests for reprints: Henry K. Wong, Henry Ford Health System, One Ford Place-4D, Detroit, MI 48202. Phone: 313-874-9171; Fax: 313-874-4851; E-mail: hwong1{at}hfhs.org.

Purpose: Mycosis fungoides (MF) is a cutaneous T-cell lymphoma (CTCL) characterized by neoplastic skin-homing T cells. To better understand the immunopathogenesis of MF, we analyzed the functional ability of peripheral blood mononuclear cells (PBMC) from early and late MF/CTCL patients to express cytokine genes. In late stage MF/CTCL, patients were separated into those with blood involvement (+B) and without blood involvement (–B).

Experimental Design: We analyzed T_H1 (interleukin 2 (IL-2), IFN-), T_H2 (IL-4, IL-5, IL-10, IL-13), and T_H17 (IL-17) cytokine gene expression from activated PBMCs from normal (n = 12), psoriasis (n = 6), early MF/CTCL (n = 11), and late MF/CTCL+B (n = 4) and MF/CTCL–B (n = 3) by quantitative real-time PCR.

Results: PBMCs from early MF/CTCL and psoriasis showed higher induction of IL-2, IL-4, and IFN- genes than those from normal and late MF/CTCL–B and MF/CTCL+B (P < 0.05) in descending order. PBMCs from late MF/CTCL–B exhibited generally the highest level of IL-5, IL-10, IL-13, and IL-17 expression compared with the other groups. PBMCs from early MF/CTCL and late MF/CTCL–B had similarly elevated IL-13 and IL-17. Of all groups, PBMCs from late MF/CTCL+B had the lowest levels of IL-2 (P < 0.05), IL-4, IFN-, IL-13, and IL-17.

Conclusions: The different pattern of cytokine gene expression suggests a change in immune function in MF/CTCL from early MF/CTCL to late MF/CTCL–B to late MF/CTCL+B. These stages are consistent with localized disease associated with an anti-tumor immune response and late MF/CTCL associated with a loss of immune function mediated by malignant T cells that share regulatory T cell–like properties.