FcγRIII activation is different in CD16+ cytotoxic T lymphocytes and natural killer cells

Abstract

The transmembrane protein CD16 (FcγRIII) 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, FcγRIII 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‐γ transcription in NK cell clones than in non‐MHC‐restricted CTL clones. Also a higher tumor necrosis factor‐α production of NK clones after CD16 cross‐linking compared to CD16^+dim CTL could be observed. These data suggest that after CD16 activationCD16^+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.