Abstract
Cytolytic T lymphocytes (CTL) were identified during the late 1960’s (1,2) and are thought to be important effector cells in immunity to viruses (3) and in allograft rejection (4), Despite considerable effort during the past decade, little has been learned about the biochemical basis for the killing event. Not only do the presumed molecular mediators remain unidentified, but fundamental physiological questions remain unanswered.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Brunner, K.T., J. Mauel, J.-C. Cerottini, H. Rudolf, and B. Chapuis. In vitro studies of cellular and humoral immunity induced by tumor allografts. In “Mechanisms of Inflammation Induced by Immune Reactions,” P.A. Miescher and P. Grabar, eds., pp. 342–357 (1967).
Berke G., G. Yagil, H. Ginsburg, and M. Feldman. Kinetic analysis of a graft reaction induced in cell culture. Immunol. 17:723–740 (1969).
Doherty, P.C., and R.M. Zinkernagel. T-cell-mediated immuno-pathology in viral infections. Transplant. Rev. 19:89–120 (1974).
Cerottini, J.-C., and K.T. Brunner. Cell-mediated cytotoxicity, allograft rejection, and tumor immunity. Adv. Irmnunol, 18:67–132 (1974).
Martz, E. Early steps in specific tumor cell lysis by sensitized mouse T lymphocytes. II. Electrolyte permeability increase in the target cell membrane concomitant with programming for lysis. J. Immunol. 117:1023–1027 (1976).
Sanderson, C.J. The mechanism of lymphocyte-mediated cytotoxicity. Biol Rev. 56:153–197 (1981).
Boyle, M.D.P., S.H. Ohaninan, and T. Borsos. Studies on the terminal stages of antibody-complement-mediated killing of a tumor cell. II. Inhibition of transformation of T to dead cells by 3’5’CAMP. J. Immunol. 116:1276–1279 (1976).
Burakoff, S.J., E. Martz, and B. Benacerraf. Is the primary complement lesion insufficient for lysis? Failure of cells damaged under osmotic protection to lyse in EDTA or at low temperature after removal of osmotic protection. Clin. Immunol, and Immunopathol. 4:108–126 (1975).
Martz, E. Mechanism of specific tumor cell lysis by allo-immune T-lymphocytes: Resolution and characterization of discrete steps in the cellular interaction. Contemp. Top. Immunobiol. 7:301–361 (1977).
Hiserodt, J.C., G.J. Tiangco, and G.A. Granger. The LT system in experimental animals. IV. Rapid specific lysis of Cr-labeled allogeneic target cells by highly unstable high MW lymphotoxin-receptor complex (es) released in vitro by activated alloimmune murine T lymphocytes. J. Immunol. 123:332–341 (1979).
Martz, E., and B. Benacerraf. Multiple target cell killing by the cytolytic T-lymphocyte and the mechanism of cytotoxicity. Transplantation 21:5–11 (1976).
Zagury, D., J. Bernard, N. Thierness, M. Feldman, and G. Berke. Isolation and characterization of individual functionally reactive cytotoxic T lymphocytes: conjugation, killing and recycling at the single cell level. Eur. J. Immunol. 5:818–822 (1975).
Golstein, P. Sensitivity of cytotoxic T cells to T-cell mediated cytotoxicity. Nature 252:81–83 (1974).
Küppers, R.C., and C.S. Henney. Evidence for direct linkage between antigen recogntion and lytic expression in effector T cells. J. Exp. Med. 143:684–689 (1976).
Bubbers, J.E., and C.S. Henney. Studies on the synthetic capacity and antigenic expression of glutaraldehyde-fixed target cells. J. Immunol. 114:1126–1131 (1975).
Thorn R.M., and C.S. Henney. Studies on the mechanism of lymphocyte-mediated cytolysis. VI. A reappraisal of the requirement for protein synthesis during T cell-mediated lysis. J. Immunol. 116:146–149 (1976).
Bevan, M.J., and M. Cohn. Cytotoxic effects of antigen-and mitogen-induced T cells on various targets. J. Immunol. 114:559–565 (1975).
Gately, M., and E. Martz. Comparative studies on the mechanisms of nonspecific. Con A-dependent cytolysis and specific T cell-mediated cytolysis. J. Immunol. 119:1711–1722 (1977).
Parker, W.L., and E. Martz. Lectin-induced nonlethal adhesions between cytolytic T lymphocytes and antigenically unrecognizable tumor cells, and nonspecific “triggering” of cytolysis. J. Immunol. 124:25–35 (1980).
Küppers, R.C., and C.S. Henney. Studies on the mechanism of lymphocyte-mediated cytolysis. IX. Relationships between antigen recognition and lytic expression in killer T cells. J. Immunol. 118:71–76 (1977).
Grimm, E., and B. Bonavida. Mechanism of cell-mediated cytotoxicity at the single cell level. I. Estimation of cytotoxic T lymphocyte frequency and relative lytic efficiency. J. Immunol. 123:2861–2869 (1979).
Golstein, P., and E.T. Smith. The lethal hit stage of mouse T and non-T cell-mediated cytolysis. Differences in cation requirements and characterization of an analytical “cation pulse” method. Eur. J. Immunol. 6:31–37 (1976).
Wagner, H., and M. Rollinghoff. T cell-mediated cytotoxicity: Discrimination between antigen recognition, lethal hit and cytolysis phase. Eur. J. Immunol. 4:745–750 (1974).
Martz, E. Early steps in specific tumor cell lysis by sensitized mouse T-lymphocytes. I. Resolution and characterization. J. Immunol. 115:261–267 (1975).
Martz, E. Immune lymphocyte to tumor cell adhesion: magnesium sufficient, calcium insufficient. J. Cell Biol. 84:584–598 (1980).
Gately, M.K., and E. Martz. Early steps in specific tumor cell lysis by sensitized mouse T lymphocytes. III. Resolution of two distinct roles for calcium in the cytolytic process. J. Immunol. 122:482–489 (1979).
Plaut, M., J.E. Bubbers, and C.S. Henney. Studies on the mechanism of lymphocyte-mediated cytolysis. VII. Two stages in the T cell-mediated lytic cycle with distinct cation requirements. J. Immunol. 116:150–155 (1976).
Golstein, P., C. Foa, and I.C.M. MacLennan. Mechanism of T-cell-mediated cytolysis: The differential impact of cyto-chalasins at the recognition and lethal hit stages. Eur. J. Immunol. 8:302–309 (1978).
Gately, M.K., and E. Martz. Inhibition of the lethal hit phase of T cell-mediated cytolysis by pharmacologic agents. Fed. Proc. 38:1166 (Abs. #4960) (1979).
Golstein, P. and E.T. Smith. Mechanism of T cell-mediated cytolysis: The lethal hit stage. Contemp. Top. Immunobiol. 7:273–300 (1977).
Martz E., C.D. Tsoukas, and W.J. Wechter. Evidence against Ca++ poisoning by killer cells: Mast cells killed by T lymphocytes do not secrete prelytically. J. Supramol. Struct. Suppl. 3:311 (Abstract 818) (1979).
Ko, L., and D. Lagunoff. Depletion of mast cell ATP inhibits complement-dependent cytotoxic histamine release. Exp. Cell Res. 100:313–321 (1976).
Henney, C.S. T cell mediated cytolysis: Consideration of the role of a soluble mediator. J. Reticuloendothelial Soc. 17:231–235 (1975).
Todd, R.F., and G. Berke. Functional characterization of membrane components of cytotoxic peritoneal exudate T lymphocytes. I. Search for T cell receptor activity in lymphocyte membrane fractions. Immunochemistry 11:313–320 (1974).
Whisnant, C.C., K.H. Singer, and D.B. Amos. Interaction of cytotoxic T lynnphocytes with target cells. I. Specific inhibition by detergent-solubilized, partially purified mouse histocompatibility anitgens. J. Immunol. 121:2253 (1978).
Todd, R.F. III, R.D. Stuiting, and D.B. Amos. Lymphocyte-mediated cytolysis of allogeneic tumor cells in vitro. I. Search for target antigens in subcellular fractions. Cellular Immunol. 18:304–323 (1975).
Nagy, Z.A., and B.E. Elliott. The receptor specificity of alloreactive T cells. Distinction between stimulator K, I, and D region products and degeneracy of third-party H-2 recognition by low-affinity T cells. J. Exp. Med. 150:1520–1537 (1979).
Linna, T.J., H.D. Engers, J.-C. Cerottini, and K.T. Brunner. Inhibition of cytolytic T lymphocyte activity with subcellular alloantigen preparations and with unlabeled allogenic target cells. J. Immunol. 120:1544–1549 (1978).
Gilmer, P.J., H.O. McDevitt, and H.M. McConnell. Inhibition of specific T cell-target cell conjugates by target cell plasma membranes. J. Immunol. 120:774 (1978).
Ozato, K., H.K. Ziegler, and C.S. Henney. Liposomes as model membrane systems for immune attack. I. Transfer of antigenic determinants to lymphocyte membranes after interactions with hapten-bearing liposomes. J. Immunol. 121:1376 (1978).
Kimura, A.K., and H. Wigzell. Cell surface glycoproteins of murine cytotoxic T lymphocytes. I. T 145, a new surface glycoprotein selectively expressed on Ly l cytotoxic T lymphocytes. J. Exp. Med. 147:1418–1434 (1978).
Berke, G., Y. Kaufmann, and D. Gabison. Cell surface determinants of cytotoxic T lymphocytes: possible role in lymphocyte-target cell interaction. Fed. Proc. 39:1198 (Abstract #4891) (1980).
Gately, M.K., and E. Martz. Til: A new protein marker on activated murine T lymphocytes. J. Immunol. 126:709–714 (1981).
Reif, A.E., and J.M. Allen. The AKR thymic antigen and its distribution in leukemias and nervous tissues. J. Exp. Med. 120:413 (1964).
Davignon, D., E. Martz, T. Reynolds, K. Kurzinger, and T.A. Springer. Lymphocyte function-associated antigen one (LFA-1): a surface antigen distinct from Lyt-2/3 that participates in T lymphocyte-mediated killing. Proc. Natl. Acad. Sci. USA 78:4535–4539 (1981).
Kimura, A.K., and H. Wigzell. Cytotoxic T lymphocyte membrane components: An analysis of structures related to function. Cont. Top. Mol. Immunol. 6:209–244 (1977).
Redelman, D., and P.E. Trefts. In vitro studies of the rabbit immune system. VIII. Rabbit anti-mouse cytotoxic T-effector cells are inhibited by anti-rabbit T-cell serum in the absence of complement. J. Immunol. 121:1532–1539 (1978).
Rabinowitz, R., and M. Schlesinger. Inhibition of the activity of cytotoxic murine T lymphocytes by antibodies to idiotypic determinants. Immunol. 39:93–99 (1980).
Kimura, A.K. Inhibition of specific cell-mediated cytotoxicity by anti-T-cell receptor antibody. J. Exp. Med. 139:888–901 (1974).
Rabinowitz, R., R. Laskov, and M. Schlesinger. Inhibition of cell-mediated lysis by xenoantibodies reactive with effector T lymphocytes. Eur. J. Immunol. 10:219–223 (1980).
Hiserodt, J.C., and B. Bonavida. Studies on the induction and expression of T cell-mediated immunity. XI. Inhibition of the “Lethal Hit” in T cell-mediated cytotoxicity by heterologous rat antiserum made against alloimmune cytotoxic T lymphocytes. J. Immunol. 126:256–262 (1981).
Platsoucas, C.D., and R.A. Good. Inhibition of specific cell-mediated cytotoxicity by monoclonal antibodies to human T cell antigens. Proc. Natl. Acad. Sci. USA 78:4500–4504 (1981).
Chang, T.W., P.C. Kung, S.P. Gingras, and G. Goldstein. Does 0KT3 monoclonal antibody react with an antigen-recognition structure on human T cells? Proc. Natl. Acad. Sci. USA 78: 1805–1808 (1981).
Tsoukas, C.D., R.I. Fox, D.A. Carson, S. Fong, and J.H. Vaughan. Monoclonal antibody 0KT3 blocks the function of human cytotoxic T-lymphocytes against autologous EBV-transformed target cells. Submitted for publication.
Reinherz, E.I., R.E. Hussey, and S.F. Schlossman. A monoclonal antibody blocking htiman T cell function. Eur. J. Immunol. 10: 758–762 (1980).
Evans, R.L., D.W. Wall, C.D. Platsoucas, F.P. Siegal, S.M. Fikrig, C.M. Testa, and R.A. Good. Thymus-dependent membrane antigens in man: inhibition of cell-mediated lympholysis by monoclonal antibodies to antigen. Proc. Natl. Acad. Sci. USA 78:544–548 (1981).
Ledbetter, J.A., R.L. Evans, M. Lipinski, C. Cunningham-Rundles, R.A. Good, and L.A. Herzenberg. Evolutionary conservation of surface molecules that distinguish T Ijmiphocyte helper/inducer and cytotoxic/suppressor subpopulations in mouse and man. J. Exp. Med. 153:310–323 (1981).
Ledbetter, J.A., and L.A. Herzenberg. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunological Rev. 47:63–89 (1979).
Nakayama, E., H. Shiku, E. Stockert, H.F. Oettgen, and L.J. Old. Cytotoxic T cells: Lyt phenotype and blocking of killing activity by Lyt antisera. Proc. Natl. Acad. Sci. USA 76:1977–1981 (1979).
Shinohara, N., and D.H. Sachs. Mouse alloantibodies capable of blocking cytotoxic T-cell function. I. Relationship between the antigen reactive with blocking antibodies and the Lyt-2 locus. J. Exp. Med. 150:432–444 (1979).
Fan, J., A. Ahmed, and B. Bonavida. Studies on the induction and expression of T cell-mediated immunity. X. Inhibition by Lyt-2, 3 antisera of cytotoxic T lymphocyte-mediated antigen-specific and nonspecific cytotoxicity: Evidence for the blocking of the binding between T lymphocytes and target cells and not the post-binding cytolytic steps. J. Immunol. 125: 2444–2453 (1980).
Shinohara, N., M. Taniguchi, and M. Kojima. Mouse alloantibodies capable of blocking cytotoxic T cell function. III. Studies of the mechanism of blocking of CML by anti-Lyt-2 antibodies. J. Immunol. 127:1575–1578 (1981).
Pierres, P., C. Goridis, and P. Golstein. Inhibition of murine T cell-mediated cytolysis and T cell proliferation by a rat monoclonal antibody immunoprecipitating two lymphoid cell surface polypeptides of 94,000 and 180,000 molecular weight. Eur. J. Immunol., in press (1981).
MacDonald, H.R., N. Thiernesse, and J.-C. Cerottini. Inhibition of T cell-mediated cytolysis by monoclonal antibodies directed against Lyt-2: heterogeneity of inhibition at the clonal level. J. Immunol. 126:1671–1675 (1981).
Ledbetter, J.A., W.E. Seaman, T.T. Tsu, and L.A. Herzenberg. Lyt-2 and Lyt-3 antigens are on two different polypeptide sub-units linked by disulfide bonds. Relationship of subunits to T cell cytolytic activity. J. Exp. Med. 153:1503–1516 (1981).
Fan, J., and B. Bonavida. Studies on the induction and expression of T cell-mediated immunity. XII. The concomitant loss and recovery of membrane-associated Lyt-2 antigens, Ijnnphocyte-target cell binding, and the antigen-specific and-nonspecific cytotoxic activity of alloimmune T lymphocytes after treatment with trypsin. J. Immunol. 127:1856–1864 (1981).
Dialynas, D.P., M.R. Loken, A.L. Glasebrook, and F.W. Fitch. Lyt-2−/Lyt-3− variants of a cloned cytolytic T cell line lack an antigen receptor functional in cytolysis. J. Exp. Mèd. 153:595–604 (1981).
Kurzinger, K., T. Reynolds, R.N. Germain, D. Davignon, E. Martz., and T.A. Springer. A novel lymphocyte function-associated antigen (LFA-1): cellular distribution, qxiantitative expression, and structure. J. Immunol. 127:596–602 (1981).
Davignon, D., E. Martz, T. Reynolds, K. Kurzinger, and T.A. Springer. Monoclonal antibody to a novel lymphocyte function-associated antigen (LFA-1). Mechanism of blockade of T lympho-cyte-mediated killing and effects on other T and B lymphocyte functions. J. Immunol. 127:590–595 (1981).
Shortman, K., and P. Golstein. Target cell recognition by cytolytic T cells: Different requirements for the formation of strong conjugates or for proceeding to lysis. J. Immunol. 123: 833–839 (1979).
Martz, E. Inability of EDTA to prevent damage mediated by cytolytic T-l3rmphocytes. Cellular Immunol. 20:304–314 (1975).
Springer, T.A. Mac-1, 2, 3, and 4: Murine macrophage differentiation antigens identified by monoclonal antibodies. In: “Heterogeneity of mononuclear phagocytes,” O. Forster, ed., Academic Press, New York. In press (1980).
Shinohara, N., U. Hammerling, and D.H. Sachs. Mouse allo-antibodies capable of blocking cytotoxic T cell function. II. Further study on the relationship between the blocking antibodies and the products of the Lyt-2 locus. Eur. J. Immunol. 10:589–594 (1980).
Hollander, N., E. Pillemer, and I.L. Weissman. The blocking effect of Lyt-2 antibodies on T cell functions. J. Exp. Med. 152:674–687 (1980).
Sarmiento, M., A.L. Glasebrook, and F.W. Fitch. IgG or IgM monoclonal antibodies reactive with different determinants on the molecular complex bearing Lyt-2 antigen block T cell-mediated cytolysis in the absence of complement. J. Immunol. 125:2665–2672 (1980).
Springer, T.A., K. Kurzinger, T. Reynolds, R.N. Germain, D. Davignon, and E. Martz. MDnoclonal antibodies as probes of surface structures participating in T lymphocyte function. In: “Monoclonal Antibodies and T Cell Hybridomas,” U. Hammerling, G. Hammerling, and J. Kearney, eds., Elsevier. In press (1981).
Golstein, P., and M. Pierres. Monoclonal antibodies as probes to study the mechanism of T cell-mediated cytolysis. Proc. 14th Leukocyte Cult. Conf., in press (1981).
Lightbody, J.J., L. Urbani, and M.D. Poulik. Effect of beta-2 microglobulin antibody on effector function of T-cell mediated cytotoxicity. Nature 250:227–228 (1974).
Golstein, P. H. Wigzell, H. Blomgren, and E.A.J. Svedmyr. Cells mediating specific in vitro cytotoxicity. II. Probable autonomy of thymus-processed lymphocytes (T cells) for the killing of allogeneic target cells. J. Exp. Med. 135:890–906 (1972).
Undah K.F., and H. Lemke. Inhibition of killer-target cell interaction by monoclonal anti-H-2 antibodies. Eur. J. Immunol. 9:526–536 (1979).
Epstein, S.L., K. Ozato, and D.H. Sachs. Blocking of allogeneic cell-mediated lympholysis by monoclonal antibodies to H-2 antigens. J. Immunol. 125:129–135 (1980).
Rothstein, T.L., M.G. Mage, J. Mond, and L.L. McHugh. Guinea pig antiserum to mouse cytotoxic T lymihocytes and their precursors. J. Immunol. 120:209 (1978).
Sullivan, K.A., G. Berke, and D.B. Amos. An antigenic determinant of cytotoxic Ijrmphocytes. Transplantation 16:388–391 (1973).
Braun, M. and F. Saal. The T-cell receptor and cytotoxicity. An anti-idiotype antiserum that inhibits a graft-versus-host reaction does not inhibit cell-mediated cytotoxicity. Cellular Immunol. 30:254–260 (1977).
Lindahl, K.F. Antisera against recognition sites: lack of effect on the mixed leucocyte culture interaction. Eur. J. Immunol. 2:501–504 (1972).
Sherman, L.A., S.J. Burakoff, and B. Benacerraf. The induction of cytolytic T lymphocytes with specificity for p-azophenyl-arsonate coupled syngeneic cells. J. Immunol. 121:1432 (1978).
Rubin, B., P. Golstein, O. Nordfang, and B. Hertel-Wulff. Generation of H-2-reactive T cell lines that bear the 5936 idiotype(s). J. Immunol. 124:161–167 (1980).
Binz, H., and H. Wigzell. Antigen-binding, idiotypic T-lympho-cyte receptors. In: “Contemporary topics in immunobiology volume 7: T cells,” O. Stutman, Ed., Plenum Press, New York, pp. 113–177 (1977).
Glasebrook, A.L. Conjugate formation by primary and secondary populations of murine immune T lymphocytes. J. Immunol. 121: 1870–1877 (1978).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1982 Plenum Press, New York
About this chapter
Cite this chapter
Martz, E., Davignon, D., Kürzinger, K., Springer, T.A. (1982). The Molecular Basis for Cytolytic T Lymphocyte Function: Analysis with Blocking Monoclonal Antibodies. In: Clark, W.R., Golstein, P. (eds) Mechanisms of Cell-Mediated Cytotoxicity. Advances in Experimental Medicine and Biology, vol 146. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-8959-0_27
Download citation
DOI: https://doi.org/10.1007/978-1-4684-8959-0_27
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-8961-3
Online ISBN: 978-1-4684-8959-0
eBook Packages: Springer Book Archive