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?
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/ml, 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 sIL-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 interleukin 2 in CTCL patients.
Dummer
R
R
Department of Dermatology, University of Würzburg Medical School, Federal Republic of Germany.
Posseckert
G
G
Nestle
F
F
Witzgall
R
R
Burger
M
M
Becker
J C
JC
Schäfer
E
E
Wiede
J
J
Sebald
W
W
Burg
G
G
D003602:Cytotoxicity, Immunologic; D006801:Humans; D007376:Interleukin-2 / Q000037:antagonists & inhibitors*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D016410:Lymphoma, T-Cell, Cutaneous / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000302:isolation & purification / Q000502:physiology*; D012878:Skin Neoplasms / Q000276:immunology*
D007376:Interleukin-2; D015375:Receptors, Interleukin-2