Dummer, Reinhard and Posseckert, Gerhard and Nestle, Frank and Witzgall, Ralph and Burger, Mathias and Becker, Jürgen C. and Schäfer, Erwin and Wiede, Johannes and Sebald, Walter and Burg, Günter
Soluble Interleukin-2 Receptors Inhibit Interleukin 2-Dependent Proliferation and Cytotoxicity: Explanation for Diminished Natural Killer Cell Activity in Cutaneous T-Cell Lymphomas In Vivo?
Journal of Investigative Dermatology 98 (1), pp. 50-54.
In patients with cutaneous T-cell lymphomas (CTCL), soluble interleukin-2 receptor serum levels (sIL-2R) were determined by ELISA technique, and natural killer cell (NK) activity, by a 4-h chromium-51 release assay. Decrease of NK activity correlated with the augmentation of serum sIL-2R. After a 4-d stimulation with interleukin 2 CTCL patients' peripheral mononuclear cells (PMC) showed an increase of cytotoxic activity similar to that in healthy donors' PMC. Normal donors' PMC demonstrated a diminished IL-2-induced cytotoxic activity in 25% CTCL serum (sIL-2R of 3000, 7330, and 10700 U/mI, respectively) compared to control serum (sIL-2R of 400, 340, and 420 U/ml, respectively). IL-2-dependent proliferation of 2-d phytohemagglutinin (PHA) blasts was lower in CTCL serum than in control serum. sIL-2R was enriched from one CTCL patient's serum by IL-2 affinity chromatography. Transfection of the Tac gene into NIH/3T3 fibroblasts resulted in the production of a recombinant sIL-2R. The presence Of enriched native or recombinant slL-2R inhibited interleukin-2-dependent generation of cytotoxic activity and PHA blast proliferation. We suggest that elevated sIL- 2R levels account for diminished NK activity by neutralizing iriterleukin 2 in CTCL patients.