ALTERATIONS IN HUMAN NATURAL-KILLER CELL-ACTIVITY AND MONOCYTE CYTO-TOXICITY INDUCED BY ZINC-DEFICIENCY

  • 1 January 1983
    • journal article
    • research article
    • Vol. 102  (4) , 577-589
Abstract
Zn deficiency alters lymphocyte and monocyte function in man and animals. A patient with isolated Zn deficiency had lymphopenia (420 lymphocytes/.mu.l), depressed T-cell mitogen response (48% of normal control), increased numbers of circulating T-suppessor cells (OKT8 reacive cells) and decreased circulating T-helper cells (OKT4 reactive cells). Activity of the patient''s natural killer (NK) cells was 1 lytic unit/106 cells (normal 10-40), and monocyte cytotoxicity (MC) was 4 times that of normal controls. Zn repletion in vivo improved the peripheral lymphocyte count, corrected the abnormal OKT8-to-OKT4 ratio, normalized T-cell response to mitogen, improved NK function and lowered MC to control values. A divalent cation chelator, 1,10-orthophenanthroline (OP), was used to simulate Zn deficiency in vitro. T-cells exposed to OP are nonresponsive to mitogen unless Zn is added. NK function of lymphocytes from normal donors exposed to OP was depressed in a time- and dose-dependent manner. NK activity of peripheral blood lymphocytes (PBL) from 12 normal donors exposed to 50 .mu.M OP for 16 h ws 10.3 .+-. 7 lytic units/106 cells (mean .+-. S.E.M. [standard error of the mean]) vs. 32.6 .+-. 14 for cells incubated in medium alone. When monocytes were exposed for 16 h to 50 .mu.M OP, MC significantly increased to a range 2-5 times that of control. OP-induced alterations of lymphocyte and monocyte function were reversed by the addition of 50 .mu.M Zn but not Ca or Mg. Since NK activity and MC may be important in host tumor immunity, alterations in Zn metabolism may have important implications for human tumor immune surveillance mechanisms.