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Blood, 15 January 2001, Vol. 97, No. 2, pp. 523-527
NEOPLASIA
Interferon resistance of cutaneous T-cell lymphoma-derived
clonal T-helper 2 cells allows selective viral replication
Reinhard Dummer,
Udo Döbbeling,
Ralf Geertsen,
Jörg Willers,
Günter Burg, and
Jovan Pavlovic
From the Department of Dermatology, University Hospital
Zurich, and the Department of Virology, University of Zurich,
Switzerland.
Cutaneous T-cell lymphomas (CTCL) comprise a heterogeneous group of
lymphoproliferative disorders that are characterized by an accumulation
of T-lymphocytes in the skin and occasionally in blood known as
Sézary syndrome (SS). In most cases the dominant clone displays
T-helper 2 cytokines. Because IFN- is a natural inhibitor of
T-helper 2 cells and IFN- is frequently used in CTCL, the impact of
IFNs on SS-derived purified clonal T-helper 2 cells was studied using
anti-V antibodies. Moreover, IFNs are known to mediate virus
resistance in normal cells. The isolated clonal CD4+ cells,
but not the nonclonal CD4+ cells, appeared resistant to
IFN- and IFN- stimulation in terms of human leukocyte antigen
up-regulation and MxA induction caused in part by alterations in Stat-1
molecule mRNA and IFNR1 mRNA transcription. The IFN resistance of
the patient-derived clonal cells was then targeted by vesicular
stomatitis virus infection after IFN- priming, resulting in
selective viral replication in clonal cells. In contrast, nonclonal
cells of the same patient showed IFN-dependent MxA expression, which is
a major mediator protein of viral protection. The IFN resistance of the
dominant T-helper 2 cells might be important for lymphomagenesis.
Interferon signaling deficiencies can be targeted for purging
patients' cells in vitro. Furthermore, this approach may allow
specific molecular interventions, resulting in the efficient treatment
of CTCL and other IFN-resistant neoplasms such as lung cancer.
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