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Basic Mechanisms of Physiologic and Aberrant Lymphoproliferation in the Skin pp 435–450Cite as

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

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Part of the book series: NATO ASI 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.

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Author information

Authors and Affiliations

  1. Department of Dermatology, University of Zurich, Zurich, Switzerland

    Reinhard Dummer, Frank Nestle & Günter Burg

  2. Department of Biochemistry, University of Würzburg, Würzburg, Germany

    Gerhard Posseckert

  3. Department of Dermatology, University of Würzburg, Würzburg, Germany

    Jurgen C. Becker

Authors
  1. Reinhard Dummer
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  2. Frank Nestle
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  3. Gerhard Posseckert
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  4. Jurgen C. Becker
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  5. Günter Burg
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Editor information

Editors and Affiliations

  1. UMD-New Jersey Medical School, Newark, New Jersey, USA

    W. Clark Lambert

  2. University of Florence, Florence, Italy

    Benvenuto Giannotti

  3. University Hospital, Utrecht, Utrecht, The Netherlands

    Willem A. van Vloten

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© 1994 Springer Science+Business Media New York

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Dummer, R., Nestle, F., Posseckert, G., Becker, J.C., Burg, G. (1994). Shedding of Interleukin-2 Receptor in Cutaneous Lymphomas: An Effective Mechanism to Circumvent Immunosurveillance?. In: Lambert, W.C., Giannotti, B., van Vloten, W.A. (eds) Basic Mechanisms of Physiologic and Aberrant Lymphoproliferation in the Skin. NATO ASI Series, vol 265. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1861-7_36

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  • DOI: https://doi.org/10.1007/978-1-4615-1861-7_36

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5756-8

  • Online ISBN: 978-1-4615-1861-7

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