Shedding of Interleukin-2 Receptor in Cutaneous Lymphomas: An Effective Mechanism to Circumvent Immunosurveillance?
Serum levels of soluble interleukin-2 receptor (sIL-2R) were determined by an ELISA technique and cytotoxic activity of peripheral mononuclear cells (PMC) measured by a four hour 51Cr release assay in patients with cutaneous T cell lymphoma (CTCL). In addition, the clinical course of these patients was followed. A significant negative correlation between serum sIL-2R and NK-activity was found (p < 0.05, n = 19). Both parameters seem to be prognostic factors for disease progression. After a four day IL-2 stimulation, the increase in cytotoxicity of CTCL PMC resembled the increase observed in control PMC. In CTCL serum, however, IL-2 dependent augmentation of cytotoxicity was reduced. IL-2 affinity chromatography of serum from one CTCL patient produced an enrichment of sIL-2R which was able to inhibit IL-2 effects.
Western blotting characterized this IL-2 inhibitor as multimeric TAC-protein (sIL-2R α-chain).
Transfection of NIH 3T3 fibroblasts resulted in production of a recombinant TAC-protein present in monomelic (45 kDa) and dimeric (90 kDa) forms.
In vitro studies revealed a dose-dependent inhibition of IL-2 induced lymphokine-activated killer cell activity and of phytohemagglutinin (PHA) blast proliferation by recombinant sIL-2R.
Our data demonstrate that sIL-2R is capable of inhibiting IL-2 dependent cell proliferation and induction of cytotoxicity. We conclude that the negative correlation between sIL-2R and NK-activity in CTCL patients may be caused by neutralization of IL-2 by sIL-2R. This could be an important mechanism for escape from immunosurveillance in lymphoma patients.
KeywordsNatural Killer Cell Activity Mycosis Fungoides Natural Killer Activity Inflammatory Skin Disease Peripheral Mononuclear Cell
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