Immune function abnormalities in peripheral blood mononuclear cell cytokine expression differentiates stages of cutaneous T-cell lymphoma/mycosis fungoides.

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(H)1 (interleukin 2 (IL-2), IFN-gamma), T(H)2 (IL-4, IL-5, IL-10, IL-13), and T(H)17 (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-gamma 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-gamma, 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.