Fc gamma RIII activation is different in CD16+ cytotoxic T lymphocytes and natural killer cells.

The transmembrane protein CD16 (Fc gamma RIII) is detected on activated macrophages, natural killer (NK) cells and a small subset of T lymphocytes. From CD3-CD56+ CD16+bright NK cells and CD3+ CD56+ CD16+dim non-major histocompatibility complex (MHC)-restricted cytotoxic T lymphocyte (CTL) clones were generated reflecting the stable, but different, CD16 expression of the respective peripheral blood subpopulations. To compare the role of CD16 on NK cells and non-MHC-restricted CTL, Fc gamma RIII activation and its mechanisms were investigated using monoclonal antibodies (mAb). Cross-linking of CD16 induced Ca2+ influx in CD16+bright NK clones. In contrast, there was no Ca2+ mobilization after CD16 activation in CD16+dim CTL, which revealed a good response to cross-linking of CD3 antigen. Pretreatment with CD16 mAb alone or cross-linked CD16 mAb did not block the CD3 response of CD16+dim CTL. Again, CD16 cross-linking induced more interferon-gamma transcription in NK cell clones than in non-MHC-restricted CTL clones. Also a higher tumor necrosis factor-alpha production of NK clones after CD16 cross-linking compared to CD16+dim CTL could be observed. These data suggest that after CD16 activation CD16+dim CTL and CD16+bright NK cells use different second messengers. In addition, signal transduction via CD3 and CD16 appears to function independently in CD16+dim non-MHC-restricted CTL.