Possible Role of Extracellular ATP in Cell-Cell Interactions Leading to CTL-Mediated Cytotoxicity

  • Frank Redegeld
  • Antonio Filippini
  • Guido Trenn
  • Michail V. Sitkovsky


The nature of the so-called lethal hit that causes target cells (TC) to die after a relatively short encounter with cytotoxic T lyphocytes (CTL) is of great interest not only to immunologists. This problem is also very challenging to those who realize that CTL-TC interactions present an interesting model system in which contacts between two different cells-(CTL) and antigen (Ag)-bearing (TC)-result in dramatic consequences for both participants: the CTL is activated due to the crosslinking of the T-cell receptor (TCR) with the Ag. whereas the TC eventually dies (Goldstein, 1987).


Lytic Effect Serine Esterase Lytic Granule Cytolytic Granule Bronte Versus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Berke G (1991): Lymphocyte-triggered internal target disintegration. Immunol Today 12: 396–399CrossRefGoogle Scholar
  2. Berke G, Rosen D (1987): Are lytic granules, and perform 1 thereof involved in lysis induced by in vivo primed peritoneal exudate CTL? Transplant Proc 19: 412–416Google Scholar
  3. Beyer EC, Steinberg TH (1991): Evidence that the gap junction protein connexin-43 is the ATP-induced pore of mouse macrophages J Biol Chem 266: 7971–7974Google Scholar
  4. Bykovskaja SN, Rytenko AN, Rauschenbach MO, Bykovsky AF (1978): Ultrastructural alteration of cytolytic lymphocytes following their interaction with target cells. II. Morphogenesis of secretory granules and intracellular vacuoles. Cell Immunol 40: 175CrossRefGoogle Scholar
  5. Di Virgilio F, Bronte V, Callavo D, Zanovello P (1989): Responses of mouse lymphocytes to extracellular adenosine 5-triphosphate (ATP). Lymphocytes with cytotoxic activity are resistant to the permeabilizing effects of ATP. J Immunol 143: 1995–1960Google Scholar
  6. Dubyak GR, Fedan JS, eds. (1990): The biological actions of extracellular ATP. Proceedings of a New York Academy of Sciences Conference, November 27–29, 1989Google Scholar
  7. Filippini A, Taffs RE, Agui T, Sitkovsky M (1990): EctoATPase activity in cytolytic T-lymphocytes protection from the cytolytic effects of extracellular ATP. J Biol Chem 265: 334–340Google Scholar
  8. Filippini A, Taffs R, Sitkovsky MV (1989): Alternative molecular mechanisms of T-cell receptor regulated effector functions of cytolytic T lymphocytes. J Immunol Immunopharmacol 9: 118–119Google Scholar
  9. Filippini A, Taffs R, Sitkovsky M (1991): Extracellular ATP in T-lymphocytes activation: Possible role in effector functions. Proc Natl Acad Sci USA 87: 82678271Google Scholar
  10. Golstein P (1987): Cytolytic T-cell melodrama. Nature 327: 12CrossRefGoogle Scholar
  11. Henkart PA, Berrebi GA, Takayama H, Munger WE, Sitkovsky MV (1987): Biochemical and functional properties of serine esterases in acid cytoplasmic granules of cytotoxic T lymphocytes. J Immunol 139: 2398–2405Google Scholar
  12. Kincaid R, Takayama H, Billingsley ML, Sitkovsky MV (1987): Differential expression of calmodulin-binding proteins in B, T lymphocytes and thymocytes. Nature 330: 176–178CrossRefGoogle Scholar
  13. Krahenbuhl O, Tschopp J (1991): Perform-induced pore formation. Immunol Today 12: 399–402CrossRefGoogle Scholar
  14. Masson D, Tschopp J (1987): A family of serine esterases in lytic granules of cytolytic T lymphocytes. Cell 49: 679–685CrossRefGoogle Scholar
  15. Ostergaard HL, Kane KP, Mesher MF, Clark WE (1987): Cytotoxic T-lymphocyte mediated lysis without release of serine esterase. Nature 330: 71–73CrossRefGoogle Scholar
  16. Pasternack MS, Eisen HN (1985): A novel serine esterase expressed by cytotoxic T lymphocytes. Nature 314: 743–745CrossRefGoogle Scholar
  17. Pasternack M, Verret CR, Liu MA, Eisen HN (1986): Serine esterase in cytolytic T lymphocytes. Nature 322: 740–743CrossRefGoogle Scholar
  18. Peters PJ, Borst J, Oorschot V, Fukuda M, Krahenbuhl O, Tschopp J, Slot JW, Geuze HJ (1991): Cytotoxic T lymphocyte granules are secretory lysosomes, contain-ing both perforin and granzymes. J Exp Med 173: 1099–1109CrossRefGoogle Scholar
  19. Podack ER, Konigsberg PJ (1984): Cytolytic T cell granules. Isolation, structural, biochemical and functional characterization. J Exp Med 160: 695–710CrossRefGoogle Scholar
  20. Podack ER, Henhgartner H, Lichtenheld MG (1991): A central role of perforin in cytolysis? Ann Rev Immunol 9: 129–157CrossRefGoogle Scholar
  21. Redegeld F, Filippini A, Sitkovsky M (1991): Comparative studies of the cytotoxic T-lymphocyte-mediated cytotoxicity and of extracellular ATP-induced cell lysis. Different requirements in extracellular Mgt+ and pH. J Immunol 147: 3638–3645Google Scholar
  22. Rozengurt E, Heppe! LA (1979): Reciprocal control of membrane permeability of transformed cultures of mouse cell lines by external and internal ATP. J Biol Chem 254: 708Google Scholar
  23. Sitkovsky MV (1988): Mechanistic, functional and immunopharmacological implications of biochemical studies of antigen receptor-triggered cytolytic T-lymphocyte activation. Immunol Rev 103: 127–160CrossRefGoogle Scholar
  24. Steinberg TH, Newman AS, Swanson JA, Silverstein SC (1987): ATP’-permeabilizes the plasm membrane of mouse macrophages to fluorescent dyes. J Biol Chem 262: 8884–8888Google Scholar
  25. Taffs RE, Sitkovsky MV (1991): Granule enyzme exocytosis assay for cytotoxic T lymphocyte activation. In: Current Protocols in Immunology Unit 3.16. Coligan JGoogle Scholar
  26. Kruisbeck AM, Margulies DH, Shevach EM, Storber W, eds. New York: John Wiley 0026 SonsGoogle Scholar
  27. Takayama H, Sitkovsky MV (1987): Antigen receptor-regulated exocytosis in cytotoxic T lymphocytes. J Exp Med 166: 725–743CrossRefGoogle Scholar
  28. Takayama H, Trenn G, Humphrey W, Bluestone JA, Henkart PA, Sitkovsky MV (1987a): Antigen receptor-triggered secretion of a trypsin-type esterase from cytotoxic T-lymphocytes. J Immunol 138: 566–569Google Scholar
  29. Takayama H, Trenn G, Sitkovsky MV (1987b): A novel cytotoxic T lymphocyte activation assay. Optimized conditions for antigen receptor triggered granule enyzme secretion. J Immunol Methods 104: 183–190CrossRefGoogle Scholar
  30. Takayama H, Trenn G, Sitkovsky MV (1988): Locus of inhibitory action of cAMP-dependent protein kinase in the antigen-receptor triggered cytotoxic T-lymphocyte activation pathway. J Biol Chem 263: 2330–2336Google Scholar
  31. Trenn G, Takayama H, Sitkovsky MV (1987): Exocytosis of cytolytic granules may not be required for target cell lysis by cytotoxic T-lymphocytes. Nature 330: 72–74CrossRefGoogle Scholar
  32. Tschopp J, Nabholz M (1990): Perforin-mediated target cell lysis by cytolytic T lymphocytes. Annu Rev Immunol 8: 279–302CrossRefGoogle Scholar
  33. Zanovello P, Bronte V, Rosato A, Pizzo P, Di Virgilio F (1990): Responses of mouse lymphocytes to extracellular ATP. II. Extracellular ATP causes cell type-dependent lysis and DNA fragmentation. J Immunol 145: 1545–1550Google Scholar

Copyright information

© Birkhäuser Boston 1993

Authors and Affiliations

  • Frank Redegeld
  • Antonio Filippini
  • Guido Trenn
  • Michail V. Sitkovsky

There are no affiliations available

Personalised recommendations