CD8(+) CD57(+) CELLS AND APOPTOSIS SUPPRESS T-CELL FUNCTIONS IN MULTIPLE-MYELOMA/

The aim of this study was to evaluate the role of CD8(+)/CD57(+) lymph ocytes in the immune dysregulation of multiple myeloma (MM). Cytofluor imetry of peripheral blood lymphocytes (PBL) purified from 39 MM patie nts showed an inverse relationship between the percentage of CD8(+)/CD 57(+) cells and CD4/CD8 ratio, Analysis of their activation antigens r evealed that they were prevalently HLA-DR+ and Fas(+). Removal of CD8( +)/CD57(+) cells from MM PBL significantly improved cell proliferation and pokeweed mitogen (PWM)-induced polyclonal Ig production in vitro, whereas the addition of supernatants from patients' CD8(+)/CD57(+) ce ll cultures to normal PBL suppressed both the PWM-driven Ig synthesis and the proliferative rate of stimulated PBL, supporting the contentio n that CD8(+)/CD57(+) cells release in vitro an inhibitory factor that is directly involved in T-cell regulatory function. However, since th e proliferative recovery of PWM-and phytohaemagglutinin (PHA)-stimulat ed MM PBL in the absence of CD8(+)/CD57(+) lymphocytes was only partia l, a dysregulated activation-induced apoptosis was anticipated, In fac t, patients' PBL displayed an increased susceptibility to apoptosis an d this was significantly enhanced after PWM and, even more, after PHA stimulation. Analysis of CD57 antigen expression on apoptotic or viabl e cells demonstrated a substantial defect of apoptosis in the CD8(+)/C D57(+) population. Our results indicate that both the immunosuppressiv e effect of CD8(+)/CD57(+) cells and the enhanced susceptibility to ap optosis of PBL could be involved in the pathogenesis of the immunodefi ciency observed in this disease.