Defective interleukin-2 induction of lymphokine-activatedkiller (LAK) activity in peripheral blood T lymphocytesof patients with monoclonal gammopathies

Abstract

SUMMARY: The recombinant interleukin-2 (rIL-2) generation of lymphokine-activated killer (LAK) cells wasinvestigated in peripheral blood T lymphocytes (PBT) of 16 patients with monoclonal gammopathyof undetermined significance (MGUS) and 32 patients with multiple myeloma (MM). LAK activitywas significantly decreased in MM. but not in MGUS patients, and was partially recovered in MM inthe remission phase. This finding was unexpected, because CD8+ CD11b+ cells, which contain LAKprecursors, are significantly increased in MM. LAK activity was investigated in purifiedCD8+ CD11b+ lymphocytes to discriminate between an intrinsic defect or a defective regulation byother T cell subsets. These cells were intrinsically unable to generate LAK activity fully followingrIL-2 stimulation. MM showed the more pronounced LAK deficiency, while MGUS patients showedintermediate values. Phenotyping revealed significantly increased proportions of Leu7+ and HLA-DR+ cells in MM patients. These data reveal another dysregulation of T cell effector functions inpatients with monoclonal gammopathies and offer further evidence of the impairment of their cell-mediated immunity.