Natural and Unnatural Killing by Cytolytic T Lymphocytes

  • K. Shortman
  • A. Wilson
Conference paper
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 126)

Abstract

Cytolytic T lymphocytes (CTL) are armed with an effective mechanism for killing target cells. Delivery of the lethal hit involves target cell recognition and conjugate formation, and is normally a highly specific process dependent on the clonally distributed, antigen-specific, and MHC-restricted T-cell receptor. The selective aspect of the recognition stage may be bypassed by adding to the cytotoxic assay a lectin (such as phytohemagglutinin [PHA] or concanavalin A [Con A]), in which case CTL will kill most target cells susceptible to the lethal hit mechanism. Until recently this seemed the only way the specificity of the T-cell receptor could be bypassed. However, there are now numerous reports of circumstances where cultured clones of mouse, rat, and human CTL lose specificity, and generally behave as if some lectin had been added to promote killing of a wide range of target cells (Shortman et al. 1983; Brooks 1983; Brooks et al. 1983; Simon et al. 1984; Teh and Yu 1983; Binz et al. 1983; Masucci et al. 1980; Santoli et al. 1981; Toribio et al. 1983; Moretta et al. 1984; van de Griend et al. 1984; Burns et al. 1984). This report summarizes our analysis of the “unnatural” or “nonspecific” killing by murine CTL, which leads us to the conclusion that two different “broad specificity” receptors may be expressed when CTL develop in culture, additional to the clonally distributed antigen-specific T-cell receptor.

Keywords

Lymphoma Sorting Prep Concanavalin 

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References

  1. Binz H, Fenner M, Frei D, Wigzell H (1983) Two independent receptors allow selective target lysism by T cell clones. J Exp Med 157: 1252–1260PubMedCrossRefGoogle Scholar
  2. Brooks CG (1983) Reversible induction of natural killer cell activity in cloned murine cytotoxic T lymphocytes. Nature 305: 155–158PubMedCrossRefGoogle Scholar
  3. Brooks CG, Urdal DL, Henney CS (1983) Lymphokine-driven “differentiation” of cytotoxic T-cell clones into cells with NK-like specificity: correlations with display of membrane macromolecules. Immunol Rev 72: 43–72PubMedCrossRefGoogle Scholar
  4. Burns GF, Triglia T, Werkmeister J A (1984) In vitro generation of human activated lymphocyte killer cells: separate precursors and modes of generation of NK-like cells and “anomolous” killer cells. J Immunol 133: 1616–1663Google Scholar
  5. Hyman R, Stallings V (1977) Analysis of hybrids between an H-2+, TL- lymphoma and an H-2+, TL+ lymphoma and its H-2+, TL+ variant subline. Immunogenetics 4: 171–181CrossRefGoogle Scholar
  6. Masucci G, Poros A, Seeley JK, Klein E (1980) In vitro generation of K562 killers in human T-lymphocyte subsets. Cell Immunol 52: 247–254PubMedCrossRefGoogle Scholar
  7. Moretta A, Pantaleo G, Mingari MC, Melioli G, Morella L, Cerottini J-C (1984) Assignment of human natural killer (NK-like) cells to the T cell lineage. Single allospecific T cell clones lyse specific or NK sensitive target cells via distinct recognition structures. Eur J Immunol 14:121–131PubMedCrossRefGoogle Scholar
  8. Santoli D, Francis MK, Trucco M (1981) Phenotypic and functional characterization of allospecific and non-specific (NK- and K-like) cytotoxic T lymphocytes generated in human mixed-lymphocyte cultures from non-cytotoxic precursors. Cell Immunol 65:230–246CrossRefGoogle Scholar
  9. Shortman K, Wilson A (1981) A new assay for cytotoxic lymphocytes, based on a radioautographic readout of mIn release, suitable for rapid, semiautomated assessment of limit-dilution cultures. J Immunol Methods 42: 135–152CrossRefGoogle Scholar
  10. Shortman K, Wilson A, Scollay R, Chen W-F (1983) Development of large granular lymphocytes with anomalous, nonspecific cytotoxicity in clones derived from Ly-2+ T cells. Proc Natl Acad Sci USA 80: 2728–2732PubMedCrossRefGoogle Scholar
  11. Shortman K, Wilson A, Scollay R (1984) Loss of specificity in cytolytic T lymphocyte clones obtained by limit dilution culture of Ly-2+ T cells. J Immunol 132: 584–593PubMedGoogle Scholar
  12. Simon MM, Weltzien HU, Buhring HJ, Eichmann K (1984) Aged murine killer T-cell clones acquire specific cytotoxicity for P815 mastocytoma cells. Nature 308: 367–370PubMedCrossRefGoogle Scholar
  13. Teh H-S, Yu M (1983) Activation of nonspecific killer cells by interleukin 2-containing supernatants. J Immunol 131: 1827–1833PubMedGoogle Scholar
  14. Toribio ML, de Landazuri MO, Lopez-Botet M (1983) Induction of NK-like cytotoxicity in cultured human thymocytes. Eur J Immunol 13: 964–969Google Scholar
  15. van de Griend RJ, Giphart MJ, van Krimpen BA, Bolhuis RLH (1984) Human T cell clones exerting multiple cytolytic activities show heterogeneity in susceptibility to inhibition by monoclonal antibodies. J Immunol 133:1222–1229PubMedGoogle Scholar
  16. Wilson A, Shortman K (1984) Degradation of specificity in cytolytic T lymphocyte clones: mouse strain dependence and interstrain transfer of nonspecific cytolysis. Eur J Immunol 14: 951–956PubMedCrossRefGoogle Scholar
  17. Wilson A, Chen W-F, Scollay R, Shortman K (1982) Semi-automated limit-dilution assay and clonal expansion of all T cell precursors of cytotoxic lymphocytes. J Immunol Methods 52: 283–306PubMedCrossRefGoogle Scholar
  18. Wilson A, Scollay R, Abbot AP, Shortman K (1984) Ly 2 positive cytotoxic T lymphocytes, whether specific or non-specific in lytic activity, may express a large granular, vacuolated lymphocyte morphology. Aust J Exp Biol Med Sci 62: 381–401PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1986

Authors and Affiliations

  • K. Shortman
    • 1
  • A. Wilson
    • 1
  1. 1.Walter and Eliza Hall Institute of Medical Research, Post OfficeRoyal Melbourne HospitalVictoriaAustralia

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