In vitro responsiveness to interleukins and theophylline of CD16+, CD56- natural killer cells in a patient with chronic granular lymphocyte disorder.

We report here the case of a 55-year-old patient with chronic granular lymphocyte disorder associated with moderate neutropenia. The majority of peripheral blood lymphocytes displayed a CD3-, CD8-, CD16+, CD56(NKH1)- phenotype. The patient's cells showed high spontaneous cytotoxic activity against K562 targets and developed the ability to kill the natural killer (NK)-resistant target Daudi following activation with interleukin 2 (IL-2). Simultaneously, IL-2 induced proliferation of these cells, albeit to a low level. The effects of IL-2 are likely to be mediated through the IL-2R beta chain (p70) which is expressed on these cells in the absence of the IL-2R alpha chain (p55, Tac). IL-4 was demonstrated to be inhibitory of both the cytotoxic and proliferative effects of IL-2. Thus, despite an unusual CD56- phenotype, the expanded lymphocyte population in this patient display functional and phenotypic properties of normal, non-activated NK cells. These cells probably represent the counterpart of a minor NK cell subpopulation, present in normal individuals at a low frequency, and which has never been fully characterized functionally. In addition, we show that the cytolytic activity of this NK cell population can be blocked in vitro in the presence of a cAMP analog or of theophylline, possibly providing new means of investigating the role of NK cell cytotoxicity on the pathogenesis of associated symptoms in such patients.