Complete molecular remission during biologic response modifier therapy forSezary 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-in vasive malignancy of CD4(+) T lymphocytes with the phenotype of mature help er T cells, Advancing stages of CTCL are associated with depressed cell-med iated immunity, increased production of T helper type 2 cytokines and decre ased levels of T helper type 1 cytokines. Objective: Our purpose was to evaluate the cytokine secretion pattern and c ell-mediated cytotoxicity in peripheral blood mononuclear cells of patients with Sezary syndrome in relation to the presence of the malignant clone. Methods: Serial polymerase chain reaction for the T-cell receptor-beta or T -cell receptor-(gamma) gene rearrangement was used to determine the presenc e of the malignant clone, Enzyme-linked immunosorbent assays were used to d etermine the levels of interleukin 4 and interferon gamma produced by the p eripheral blood mononuclear cells from the patients with Sezary syndrome. Results: We demonstrate 3 cases of Sezary syndrome with typically suppresse d cell-mediated cytotoxicity, elevated production of interleukin 4, and dep ressed production of interferon gamma by their peripheral blood mononuclear cells before institution of therapy with biologic response modifier therap y. In all 3 cases after clinical and molecular remission, we observed strik ing immunologic changes, including an increase in levels of natural killer cell activity and interferon gamma production and decreased production of i nterleukin 4. Conclusions: The observation that the cytokine secretion pattern by periphe ral blood mononuclear cells from 3 patients with Sezary syndrome normalized with the disappearance of the malignant clone from the peripheral blood su ggests that the malignant T cells account for the aberrant cytokine product ion. Moreover, the aberrant cytokine production may be the cause for suppre ssion of cell-mediated immunity seen in advancing stages of CTCL.