Absence of responsiveness to interferon-γ 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 childhood lymphohistiocytic syndrome (LHS), we investigated the number and cytolytic functions of circulating NK cells in 10 LHS children using flow cytometry, 51Cr-release and single-cell assays. In the active phase, the numbers of CD16+ or CD56+ cells and NK activity were normal in more than half of the patients or otherwise decreased. Despite the treatment with interferon-gamma (IFN-gamma) there was no significant increase 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 control values changed from 45.5% +/- 8.5% to 54.2% +/- 10.1% after the stimulation. However, the NK cells normally responded to interleukin 2 (IL-2). In contrast, NK cells from 9 patients with infectious mononucleosis (IM) responded well to both IFN-gamma and IL-1 (P < 0.01). At the single-cell level, their NK cells had defective recycling capacity with normal killing capacity. The maximal recycling capacity (MRC) values (mean +/- S.D.) were 3.6 +/- 0.8 as compared to the control value of 5.5 +/- 0.9 (P < 0.01). Two of the patients studied had extremely high 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 stimulated 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 abnormality of NK cells in LHS.