Natural killer cell immunodeficiency in patients with chronic myelogenous leukemia. III. Defective interleukin‐2 production by t‐helper and natural killer cells

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Abstract
Even though they possess normal to increased numbers of circulating natural killer (NK) cells, patients with chronic myelogenous leukemia (CML) have a functional NK‐cell deficiency which is restorable in vitro in the presence of recombinant IL‐2. We therefore measured the level of IL‐2 production by both T‐helper and NK cells from CML patients as compared to normal controls using PHA‐stimulated peripheral blood mononuclear cells (PBMs) as well as FACS‐sorted CD4+ (OKT4+) lymphoid cells and FACS‐sorted CD16+(B73.1+) lymphoid cells. Peripheral blood mononuclear cells from CML patients demonstrated markedly defective IL‐2 production as compared to normal controls (4.0 ± 1.6 and 5.9 ± 1.4 units/ml after 24 hr of 5 and 10 μg/ml PHA stimulation as compared with 40.7 ± 10.3 and 69.3 ± 15.1 units/ml for normal subjects). In addition to the decreased relative percentage of CD4+ (OKT4+) lymphoid cells in CML patients, FACS‐sorted CD4+ (OKT4+) cells also demonstrated a significant defect in IL‐2 production, (10.8 ± 3.6 units/ml as compared to 39.0 ± 5.8 units/ml after 24 hr stimulation with 10 μg/ml PHA). FACS‐sorted CD16+ (B73.1+) lymphoid cells from CML patients also demonstrated significantly decreased IL‐2 production after 24 hr incubation with increasing concentrations of PHA or with the NK‐sensitive target K562 as compared to normal controls. Defective IL‐2 production by PBMs, CD4+(OKT4+), and CD16+(B73.1+) cells from CML patients was also evident after 48 hr of PHA stimulation. Although the percentages of both T4+2H4+ and T4+4B4+ subsets are significantly decreased in CML patients, CML patients have normal ratios of T4+4B4+/T4+2H4+ subsets as compared to normal controls. These and previous results support the hypothesis that decreased IL‐2 production by both T‐helper and NK cells from CML patients may be mechanistically related to the observed NK‐cell immunodeficiency in CML patients.