High frequency of immune dysfunctions in asbestos workers and in patients with malignant mesothelioma

Abstract

We have examined the primary immune responses, the numbers of total T (T11⁺) cells, T-helper (T4⁺) cells, T-suppressor (T8⁺) cells, and natural killer (NK) (Leu7⁺) cells, in 118 healthy control subjects and compared the data to those obtained from 20 patients with clinically diagnosed malignant mesothelioma and 375 long-term asbestos workers without neoplasia. The absolute numbers of total T (T11⁺) and T-helper (T4⁺) cells were normal in asbestos workers without neoplasia but were significantly reduced in patients with mesothelioma. T-suppressor (T8⁺) cells, on the other hand, remained unchanged in the patients but were significantly elevated among the asbestos workers. This resulted in a marked reduction in T-helper (Th) to T-suppressor (Ts) ratios in mesothelioma patients and in asbestos workers. Seventy percent of the mesothelioma patients (14 of 20) had significantly depressed NK-cell activity which could be augmented but not normalized by coincubation in patients' peripheral blood lymphocytes (PBL) with interferon (IFN). Among the asbestos workers three distinctive subgroups could be identified: heightened (H-NK), normal (N-NK), and low (L-NK) NK activity. The NK activity of the L-NK group could be stimulated but not normalized by coincubation with IFN, a finding closely resembling that in malignant mesothelioma patients. Phenotyping of the circulating NK cells revealed a unique Leu7⁺ subset in increased numbers with a brightly fluorescent property in stable mesothelioma patients with relatively stable or slowly progressive disease and in more than 30% of the asbestos workers. The reduced Th/Ts ratio and NK-cell function among these asbestos workers at high risk may be a direct consequence of asbestos exposure and might not be related to neoplastic processes.