Complete molecular remission during biologic response modifier therapy for Sézary syndrome is associated with enhanced helper T type 1 cytokine production and natural killer cell activity

Background: Cutaneous T-cell lymphoma (CTCL) is a clonally derived, skin-invasive malignancy of CD4+ T lymphocytes with the phenotype of mature helper T cells. Advancing stages of CTCL are associated with depressed cell-mediated immunity, increased production of T helper type 2 cytokines and decreased levels of T helper type 1 cytokines. Objective: Our purpose was to evaluate the cytokine secretion pattern and cell-mediated cytotoxicity in peripheral blood mononuclear cells of patients with Sézary syndrome in relation to the presence of the malignant clone. Methods: Serial polymerase chain reaction for the T-cell receptor-β or T-cell receptor-γ gene rearrangement was used to determine the presence of the malignant clone. Enzyme-linked immunosorbent assays were used to determine the levels of interleukin 4 and interferon gamma produced by the peripheral blood mononuclear cells from the patients with Sézary syndrome. Results: We demonstrate 3 cases of Sézary syndrome with typically suppressed cell-mediated cytotoxicity, elevated production of interleukin 4, and depressed production of interferon gamma by their peripheral blood mononuclear cells before institution of therapy with biologic response modifier therapy. In all 3 cases after clinical and molecular remission, we observed striking immunologic changes, including an increase in levels of natural killer cell activity and interferon gamma production and decreased production of interleukin 4. Conclusions: The observation that the cytokine secretion pattern by peripheral blood mononuclear cells from 3 patients with Sézary syndrome normalized with the disappearance of the malignant clone from the peripheral blood suggests that the malignant T cells account for the aberrant cytokine production. Moreover, the aberrant cytokine production may be the cause for suppression of cell-mediated immunity seen in advancing stages of CTCL. (J Am Acad Dermatol 2001;45:208-16.)