Eur. J. Immunol. 1992. 22: 1635-1638
CD16 in T lymphocytes and NK cells
1635
Short paper Peter Uciechowski, J. Engelbert Gessner, Ralf SchindlerA and Reinhold E. Schmidt
FcyRIII activation is different in CD16+ cytotoxic T lymphocytes and natural killer cells*
Abteilung fur Immunologie, Transfusionsmedizin und NephrologieA, Zentrum Innere Medizin und Dermatologie, Hannover
The transmembrane protein CD16 (FcyRIII) is detected on activated macrophages, natural killer (NK) cells and a small subset o f T lymphocytes. From CD3CD56+ CD16+br1ght NK cells and CD3+ CD56+ CD16+d11n 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 CDl6 on NK cells and non-MHC-restricted CTL, FcyRIII activation and its mechanisms were investigated using monoclonal antibodies (mAb). Cross-linking of CD16 induced Ca2+ influx in CD16+"rig'1t NK clones. I n contrast, there was no Ca2+mobilization after CD16 activation in CD16+d1mCTL, 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+d1mCTL. Again, CD16 cross-linking induced more interferon-y transcription in NK cell clones than in non-MHC-restricted CTL clones. Also a higher tumor necrosis factor-a production of NK clones after CD16 cross-linking compared to CD16+d1m CTL could be observed. These data suggest that after CD16 activation CD16+"1mCTL and CD16+""ght NK cells use different second messengers. In addition, signal transduction via CD3 and CD16 appears to function independently in CDlbfdlrn non-MHC-restricted CTL.
1 Introduction The human Fc receptor with low affinity for IgG (FcyRIII, CD16) has bcen described in peripheral blood on monocytes, polymorphonuclear cells (PMN), and NK cells. FcyRIlI is expressed as result of two different genes either as a glycosyl-phosphoinositol-anchored form on PMN, or as a transmembrane molecule on monocytes and NK cells [1, 21. In addition to typical CD3- CD56+ NK lymphocytes there is a small Tcell subset expressing CD16 antigen in a lower density [ 3 , 41. The majority of these cells is TcR y6+ CD4- C D S , mediates non-MHC-restricted cytotoxicity, and cxerts antibody-dependent cell-mediated cytotoxicity (ADCC) functions [S]. Although CD16 expression and ADCC activity are lower than with NK cells these y6+ CTL reach similar levels of non-MHC-restricted cytotoxicity upon stimulation with IL-2 [S,6].The FcyRIII activation on TcR ctD+ lymphocytes co-expressing CD16 antigen and the potential interaction of both complexes has not been studied yet. From previous studies CD16 is known to be involved in signal transduction of NK cells and PMN, e.g. triggering of cytotoxicity, phosphoinositide turnover and calcium mobilization [7-9]. Cross-linking of CD16 ligands on NK cells has also been reported to induce transcription of cytokine genes for IFN-y and TNF-a [8, 101. Recent
[I 100681
*
This work was supported by thc Dcutsche Forschungsgemeinschaft, DFG Schm 596/2-2 and a postgraduate program by thc slate of Nicdersachsen (P.U., J.E.G.).
Correspondence: Reinhold E. Schmidt, Abtcilung fur Immunologic und Traiisfusionsmcdiziii, Mcdizinische Hochschule Hannover, Konstanty-Gutschow-Str. 8, D-3000 Hannover 61, FRG
0 VCH Vcrlagsgescllschaft mbH, D-6940 Wcinhcim, 1992
reports made clear that NK cells share the chain as signal transducing molecule withT cells.The CD3
CD16 in T lymphocytes and NK cells
1635
Short paper Peter Uciechowski, J. Engelbert Gessner, Ralf SchindlerA and Reinhold E. Schmidt
FcyRIII activation is different in CD16+ cytotoxic T lymphocytes and natural killer cells*
Abteilung fur Immunologie, Transfusionsmedizin und NephrologieA, Zentrum Innere Medizin und Dermatologie, Hannover
The transmembrane protein CD16 (FcyRIII) is detected on activated macrophages, natural killer (NK) cells and a small subset o f T lymphocytes. From CD3CD56+ CD16+br1ght NK cells and CD3+ CD56+ CD16+d11n 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 CDl6 on NK cells and non-MHC-restricted CTL, FcyRIII activation and its mechanisms were investigated using monoclonal antibodies (mAb). Cross-linking of CD16 induced Ca2+ influx in CD16+"rig'1t NK clones. I n contrast, there was no Ca2+mobilization after CD16 activation in CD16+d1mCTL, 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+d1mCTL. Again, CD16 cross-linking induced more interferon-y transcription in NK cell clones than in non-MHC-restricted CTL clones. Also a higher tumor necrosis factor-a production of NK clones after CD16 cross-linking compared to CD16+d1m CTL could be observed. These data suggest that after CD16 activation CD16+"1mCTL and CD16+""ght NK cells use different second messengers. In addition, signal transduction via CD3 and CD16 appears to function independently in CDlbfdlrn non-MHC-restricted CTL.
1 Introduction The human Fc receptor with low affinity for IgG (FcyRIII, CD16) has bcen described in peripheral blood on monocytes, polymorphonuclear cells (PMN), and NK cells. FcyRIlI is expressed as result of two different genes either as a glycosyl-phosphoinositol-anchored form on PMN, or as a transmembrane molecule on monocytes and NK cells [1, 21. In addition to typical CD3- CD56+ NK lymphocytes there is a small Tcell subset expressing CD16 antigen in a lower density [ 3 , 41. The majority of these cells is TcR y6+ CD4- C D S , mediates non-MHC-restricted cytotoxicity, and cxerts antibody-dependent cell-mediated cytotoxicity (ADCC) functions [S]. Although CD16 expression and ADCC activity are lower than with NK cells these y6+ CTL reach similar levels of non-MHC-restricted cytotoxicity upon stimulation with IL-2 [S,6].The FcyRIII activation on TcR ctD+ lymphocytes co-expressing CD16 antigen and the potential interaction of both complexes has not been studied yet. From previous studies CD16 is known to be involved in signal transduction of NK cells and PMN, e.g. triggering of cytotoxicity, phosphoinositide turnover and calcium mobilization [7-9]. Cross-linking of CD16 ligands on NK cells has also been reported to induce transcription of cytokine genes for IFN-y and TNF-a [8, 101. Recent
[I 100681
*
This work was supported by thc Dcutsche Forschungsgemeinschaft, DFG Schm 596/2-2 and a postgraduate program by thc slate of Nicdersachsen (P.U., J.E.G.).
Correspondence: Reinhold E. Schmidt, Abtcilung fur Immunologic und Traiisfusionsmcdiziii, Mcdizinische Hochschule Hannover, Konstanty-Gutschow-Str. 8, D-3000 Hannover 61, FRG
0 VCH Vcrlagsgescllschaft mbH, D-6940 Wcinhcim, 1992
reports made clear that NK cells share the chain as signal transducing molecule withT cells.The CD3
