Immunology Today, Vol. 1I, No. 8 199U
osfr 24 Cucoa-Belvedere, M.. Monafo. V., Martinetti, M. et aL
(1989) T~ssueAntlgens 34. 127-132 25 Dawkins, R.L., Martin, E., Cobain, TJ., Kay, P.H. and Christiansen, F.T. (1987)in New Approaches to Genetic D,.seases(Sasazuk~,T., ed.), pp. 69-77, Academic Press 26 Dawkins, R.L., Martin, E., Saueracker, G. et aL (1990) j. Autoimmun. 3. 66-83 27 Schaffe,, F.M., Pa!ermos, J., Zhu, Z.B. eta/. (1989) Proc. Natl Acad. So. USA 86, 8015-8019 211 Tokunaga, K., Saueracker, G., Kay, P.H. etaL (1988) J. Exp. Med. 168, 933-940 29 Zhang. WJ., Degli-Es3osti, M.A., Cobain, T.J. et aL J. Exp. Med (in press) O'Garra, A., Umland, 3, De France, r. and Christiansen, J. (1988) Immuno!. Today 9, 45--54 31 Ochs, H.D, Wedgwood, R.J., Heller, S.R. and Beatty, P.G. (1986) Ctin lmmunoL lmmunopathol. 40, 94-104 Bottger, E.C. and Bitter-Suermann, D. (1987) !mmunol. Today 8, 261-264 Peters, M.G., Ambrus, J.R., Fauci, A.S. and Brown, E.J. (1988)J. Exp. Med. 168, 1225-1235 34 Kehrl, J.H., Miqer, A. and Fauci, A.S. (1987) J. Exp. Med. 166, 786-791 Zo!a, H. and Nikoloutsopoulos, A. (1989)Immunology 67, 231_236 36 Da Silva, F.P., Hoecker, G.F.. Day, N.K., Vienne, K and Rubinstein, P. (1978) Proc. N~tlAcad. 5cL USA 75, 963-965 37 Melchers, F., Erdei, A., Schulz, T. and Dierich, M.P. (1985} Nature 317,264-267
Extracellular
ATP as a possiblemediatorof ceil-mediatedcytotoxicity
Cytotoxic T lymph_&-ytes (CTL,I and natural killer (NK) cells !yse target" cells by a specialized mechanism that involves the release of soluble 'killer' mediators. While several possible mediators have ~een demonstrated, it is likely that others have yet to be identified. For more than two decades it has been known that exogenous A TPis lytic to many cell ,types.In this article Francesco Di Virgilio and colleagues propose that extracellular A TPmay be a mediator of cytotoxic cell-dependent lysis. The molecular mechanism of cell !ysls mediate,J by CTL is poorly understood. It is known that close contact between effector and target cell (TC) plasma membranes is required and that, once the lethal hit has been delivered, the TC is irreversibly committed to death while the effector can move away and a~ack another target. Several early alterations occurring in TCs injured by CTL have been described (swelling, depolarization of plasma membrane potential, increase in cytosolic free Ca2~- ([Ca2÷],), release of low molecular weight intracellular solutes and degradation of DNA), although it is debatable whether or not these alterations are causally related to TC lysis ~' A number of soluble mediators of T-cell-mediated lysis have been proposed: perforins, serine esterases, lympho-
' CNRCenterfor the Studyof the Physiologyof Mitochondria,Instituteof GeneralPathology,Via Trieste75,1-35131,Padova,Italy.2Laboratoryof Immunology, Institute of Ontology, Via Gattamelata 64, 1-35128, Padova,Itaiy. 274
38 Daha, M.R., Bloem, A.C. and Ballieux, R.E. (1984) J. Immunol. 132, 1197-1201 39 Bird, P. and Lachmann, P.J. (1988) Eur. J. ImmunoL 18, 1217-1222 Spies, T., Blanck, G., Bresnahan, M., Sands, J. and Strominger, J.L. (1989) Science 243, 214-217 41 Tsuge, I., Shen, F-W., Steinmetz, M. and Boyse, E.A. ',1987) lmmunogenetics 26, 376-380 42 Oxelius, V.A. (1984) Am. J. Med. 76, 7-18 43 Hashirnoto, S., Michalski, J.P., Berman, M.A. and McCombs, C. (1990) Clin. Exp. Immunol. 79, 227-232 44 Dinarello, CA., Cannon, J.G., Wolf, S.M. etaL (1986) J. Exp. Med. 163, 1433-1450 45 Bacle, F., Haeffner-Cavaillon, N., Laude, M., Couturier, C. and Kazat,:hkine, M.D. (1990) J. ImmunoL 144, 147-152 Koyc-na, N., Harada, N., Takahashi, T. et aL (1988) Immunology 63, 277-283 47 Heikkila, M., Koistinen, J., Lohman, M and Koskimies, S. (1984) TissueAntigens 23, 280-283 Cunningham-Rundles, C., Brandeis, W.E., Pudifin, D.J., Day, N.K. and Good, R.A. (1981) Clin. Exp. Immunol. 45, 299-304 49 Asquith, P. (i 974) Clin. GastroenteroL 3, 213-234 50 Alper, C.A., Marcus, D., Truedson, L. etaL (1987) Complement 4, 125 51 Gordon, C., Ranges, G.E., Greenspan, J.S. and Wofsy, D. (1989) Clin. Immunol. Immunopathol. '-2, 421-434 52 Shalaby, M.R., Aggarwal, B.B., Rinderknecht, E. et aL (1985) J. ImmunoL 135, 2069-2073
Fr cesco Di Virgilio Paola Pizzo , Paola Zanovelloz, Vincenzo Brontez and Dino Collavoz toxins, tumor necrosis factor (TNF), NI
osfr 24 Cucoa-Belvedere, M.. Monafo. V., Martinetti, M. et aL
(1989) T~ssueAntlgens 34. 127-132 25 Dawkins, R.L., Martin, E., Cobain, TJ., Kay, P.H. and Christiansen, F.T. (1987)in New Approaches to Genetic D,.seases(Sasazuk~,T., ed.), pp. 69-77, Academic Press 26 Dawkins, R.L., Martin, E., Saueracker, G. et aL (1990) j. Autoimmun. 3. 66-83 27 Schaffe,, F.M., Pa!ermos, J., Zhu, Z.B. eta/. (1989) Proc. Natl Acad. So. USA 86, 8015-8019 211 Tokunaga, K., Saueracker, G., Kay, P.H. etaL (1988) J. Exp. Med. 168, 933-940 29 Zhang. WJ., Degli-Es3osti, M.A., Cobain, T.J. et aL J. Exp. Med (in press) O'Garra, A., Umland, 3, De France, r. and Christiansen, J. (1988) Immuno!. Today 9, 45--54 31 Ochs, H.D, Wedgwood, R.J., Heller, S.R. and Beatty, P.G. (1986) Ctin lmmunoL lmmunopathol. 40, 94-104 Bottger, E.C. and Bitter-Suermann, D. (1987) !mmunol. Today 8, 261-264 Peters, M.G., Ambrus, J.R., Fauci, A.S. and Brown, E.J. (1988)J. Exp. Med. 168, 1225-1235 34 Kehrl, J.H., Miqer, A. and Fauci, A.S. (1987) J. Exp. Med. 166, 786-791 Zo!a, H. and Nikoloutsopoulos, A. (1989)Immunology 67, 231_236 36 Da Silva, F.P., Hoecker, G.F.. Day, N.K., Vienne, K and Rubinstein, P. (1978) Proc. N~tlAcad. 5cL USA 75, 963-965 37 Melchers, F., Erdei, A., Schulz, T. and Dierich, M.P. (1985} Nature 317,264-267
Extracellular
ATP as a possiblemediatorof ceil-mediatedcytotoxicity
Cytotoxic T lymph_&-ytes (CTL,I and natural killer (NK) cells !yse target" cells by a specialized mechanism that involves the release of soluble 'killer' mediators. While several possible mediators have ~een demonstrated, it is likely that others have yet to be identified. For more than two decades it has been known that exogenous A TPis lytic to many cell ,types.In this article Francesco Di Virgilio and colleagues propose that extracellular A TPmay be a mediator of cytotoxic cell-dependent lysis. The molecular mechanism of cell !ysls mediate,J by CTL is poorly understood. It is known that close contact between effector and target cell (TC) plasma membranes is required and that, once the lethal hit has been delivered, the TC is irreversibly committed to death while the effector can move away and a~ack another target. Several early alterations occurring in TCs injured by CTL have been described (swelling, depolarization of plasma membrane potential, increase in cytosolic free Ca2~- ([Ca2÷],), release of low molecular weight intracellular solutes and degradation of DNA), although it is debatable whether or not these alterations are causally related to TC lysis ~' A number of soluble mediators of T-cell-mediated lysis have been proposed: perforins, serine esterases, lympho-
' CNRCenterfor the Studyof the Physiologyof Mitochondria,Instituteof GeneralPathology,Via Trieste75,1-35131,Padova,Italy.2Laboratoryof Immunology, Institute of Ontology, Via Gattamelata 64, 1-35128, Padova,Itaiy. 274
38 Daha, M.R., Bloem, A.C. and Ballieux, R.E. (1984) J. Immunol. 132, 1197-1201 39 Bird, P. and Lachmann, P.J. (1988) Eur. J. ImmunoL 18, 1217-1222 Spies, T., Blanck, G., Bresnahan, M., Sands, J. and Strominger, J.L. (1989) Science 243, 214-217 41 Tsuge, I., Shen, F-W., Steinmetz, M. and Boyse, E.A. ',1987) lmmunogenetics 26, 376-380 42 Oxelius, V.A. (1984) Am. J. Med. 76, 7-18 43 Hashirnoto, S., Michalski, J.P., Berman, M.A. and McCombs, C. (1990) Clin. Exp. Immunol. 79, 227-232 44 Dinarello, CA., Cannon, J.G., Wolf, S.M. etaL (1986) J. Exp. Med. 163, 1433-1450 45 Bacle, F., Haeffner-Cavaillon, N., Laude, M., Couturier, C. and Kazat,:hkine, M.D. (1990) J. ImmunoL 144, 147-152 Koyc-na, N., Harada, N., Takahashi, T. et aL (1988) Immunology 63, 277-283 47 Heikkila, M., Koistinen, J., Lohman, M and Koskimies, S. (1984) TissueAntigens 23, 280-283 Cunningham-Rundles, C., Brandeis, W.E., Pudifin, D.J., Day, N.K. and Good, R.A. (1981) Clin. Exp. Immunol. 45, 299-304 49 Asquith, P. (i 974) Clin. GastroenteroL 3, 213-234 50 Alper, C.A., Marcus, D., Truedson, L. etaL (1987) Complement 4, 125 51 Gordon, C., Ranges, G.E., Greenspan, J.S. and Wofsy, D. (1989) Clin. Immunol. Immunopathol. '-2, 421-434 52 Shalaby, M.R., Aggarwal, B.B., Rinderknecht, E. et aL (1985) J. ImmunoL 135, 2069-2073
Fr cesco Di Virgilio Paola Pizzo , Paola Zanovelloz, Vincenzo Brontez and Dino Collavoz toxins, tumor necrosis factor (TNF), NI
