ABSENCE OF RESPONSIVENESS TO INTERFERON-GAMMA BUT NOT TO INTERLEUKIN-2 AND DEPRESSED RECYCLING AS NATURAL-KILLER-CELL ABNORMALITIES IN CHILDHOOD LYMPHOHISTIOCYTIC SYNDROME

To characterize the abnormalities of natural killer (NK) cells in chil dhood lymphohistiocytic syndrome (LHS), we investigated the number and cytolytic functions of circulating NK cells in 10 LHS children using flow cytometry, Cr-61-release and single-cell assays. In the active ph ase, the numbers of CD16+ or CD56+ cells and NK activity were normal i n more than half of the patients or otherwise decreased. Despite the t reatment with interferon-gamma (IFN-gamma) there was no significant in crease in NK activity in the children with LHS: the values (mean +/- S .D.) of 32.2% +/- 14.2% became 35.0% +/- 13.3% (P > 0.05) when the con trol values changed from 45.5% +/- 8.5% to 54.2% +/- 10.1% after the s timulation. However, the NK cells normally responded to interleukin 2 (IL-2). In contrast, NK cells from 9 patients with infectious mononucl eosis (IM) responded well to both IFN-gamma and IL-2 (P < 0.01). At th e single-cell level, their NK cells had defective recycling capacity w ith normal killing capacity. The maximal recycling capacity (MRC) valu es (mean +/- S.D.) were 3.6 +/- 0.8 as compared to the control value o f 5.5 +/- 0.9 (P < 0.01). Two of the patients studied had extremely hi gh levels of serum IFN-gamma (9.8 U/ml and 158.0 U/ml) as compared to the control value of < 0.4 U/ml. NK cells may have been strongly stimu lated by IFN-gamma in vivo, which probably yields superficially normal NK cell activity in the face of the absence of responsiveness to IFN- gamma but not to IL-2. The defective recycling may be another abnormal ity of NK cells in LHS.