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Shedding of Interleukin-2 Receptor in Cutaneous Lymphomas: An Effective Mechanism to Circumvent Immunosurveillance?

  • Reinhard Dummer
  • Frank Nestle
  • Gerhard Posseckert
  • Jurgen C. Becker
  • Günter Burg
Part of the NATO ASI Series book series (NSSA, volume 265)

Abstract

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.

Keywords

Natural Killer Cell Activity Mycosis Fungoides Natural Killer Activity Inflammatory Skin Disease Peripheral Mononuclear Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Reinhard Dummer
    • 1
  • Frank Nestle
    • 1
  • Gerhard Posseckert
    • 2
  • Jurgen C. Becker
    • 3
  • Günter Burg
    • 1
  1. 1.Department of DermatologyUniversity of ZurichZurichSwitzerland
  2. 2.Department of BiochemistryUniversity of WürzburgWürzburgGermany
  3. 3.Department of DermatologyUniversity of WürzburgWürzburgGermany

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