IntroductionPrimary cutaneous lymphomas are the second most common group of extranodal non-Hodgkin lymphomas after primary gastrointestinal lymphomas. 1 They have highly characteristic clinical features and are considered prototype malignancies because they can be recognized clinically very early. In addition, because of their locations, they are well accessible for the study of immune and molecular biology. Most cutaneous lymphomas are low-grade T-cell lymphomas such as mycosis fungoides and Sézary syndrome (SS). 2 These neoplasms are not curable, even using aggressive chemotherapy and radiotherapy. 3 The malignant lymphocytes mostly express the T-cell markers CD2, CD3, CD4, and CD5. Often they lack CD7, and they display T-helper 2 (Th2) cytokines such as IL-5 and IL-10 and express the IFN-␥ receptor chain 2 (IFN␥R2). 4 IFN-␣, alone or in combination with retinoids or psoralen plus ultraviolet A irradiation, is helpful, especially in early disease. 5 Interferons are known for their pleiotropic effects. Besides the up-regulation of major histocompatibility complex molecules and the inhibition of cell proliferation and tumor growth, IFN can induce resistance to viral replication in all cells. 6 Interferons exert their effects by inducing overlapping sets of effector proteins through specific cell surface receptors (IFN␣R and IFN␥R). In this context, a cross-talk between IFN-␥ and IFN-␣/ signaling components has been reported recently. 7 It has been shown that the IFN␣R1 chain favors the association of the IFN␥R1 and the IFN␥R2 chains.Because of the beneficial clinical impact of IFN-␣ and the inhibitory potential of IFN-␥ on benign human and murine Th2 lymphocytes, 8 we studied the effects of IFNs on CTCL-derived tumor cells purified by FACS-sorting from the peripheral blood of 4 patients with SS. 4 This subtype of cutaneous T-cell lymphoma is characterized by an accumulation of malignant T-lymphocytes in skin and peripheral blood. 2 Furthermore, we evaluated the susceptibility of these SS cells to viral infections with vesicular stomatitis virus (VSV).
Patients and methods
PatientsSS was diagnosed using standard clinical criteria (erythroderma, lymphadenopathy), histologic criteria (subepidermal lymphoid infiltrate showing strong epidermotropism and expressing a T-helper cell phenotype), hematologic criteria (more than 1000 SS cells/mL), and an elevated CD4-CD8 ratio. 9-12 All patients were seronegative for human T-cell lymphocytic virus-I antibodies by enzyme-linked immunosorbent assay. Of the 4 patients whose T-cell clones were identified and investigated, 2 were in stage III (T 4 N 1 M 0) and 2 were in stage IVa (T 4 N 3 M 0 ) disease. 13 They did not receive any systemic therapy in the last 4 weeks before blood was taken. However, topical steroids had to be applied to control itching.Molecular biology studies for the T-cell receptor ␥ chain, 14 Southern blot analysis, or both documented the presence of a dominant T-cell clone in the peripheral blood of all patients. In all patients, a dominant CD4 ϩ V ϩ (do...