Skip to main content
SpringerLink
Log in

Subpopulations of Cytotoxic T Lymphocytes with Different Cytotoxic Mechanisms

  • Chapter
Book cover Cytotoxic Cells: Recognition, Effector Function, Generation, and Methods

  • 126 Accesses

Abstract

Subpopulations of T lymphocytes have been identified based on (1) expression of CD4 or CD8 accessory molecules on the cell surface [CD4+ cells generally recognize antigen (Ag) presented in the context of class II major histocompatibility complex (MHC) molecules, while CD8+ cells generally recognize Ag presented in the context of class I MHC molecules], (2) the structure of their T-cell receptor (TCR) (α/β versus γ/δ), (3) the array of lymphokines that the cells produce, and (4) functional characteristics. T-cell functions in heterogeneous populations of T cells appeared to be correlated with the expression of CD4 or CD8 molecules on the T-cell surface. Thus, T-cell-mediated cytotoxicity was associated with CD8+ T cells, while T-cell-mediated helper functions appear to reside primarily in the CD4+ T cells. However, it is now generally accepted that cytotoxic activity is not restricted to CD8+ T cells. The lytic activity of cells bearing the γ/δ TCR is well established. The extent of expression of cytotoxicity among the members of CD4+ subsets is still controversial. In this review, we summarize recent observations regarding the expression of cytotoxic activity among T-cell subsets bearing CD4 molecules. In addition, we explore the growing body of evidence indicating that cytotoxic activity expressed by lymphocytes within different T-cell subpopulations may be accomplished through distinct and independent mechanisms.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abrams SI, Russel JH (1991): CD4+ T lymphocyte-induced target cell detachment. A model for T cell-mediated lytic and nonlytic inflammatory processes. J Immunol 146: 405–413

    Google Scholar 

  • Acha-Orbea H, Scarpellino L, Hertig S, Dupuis M, Tschopp J (1990): Inhibition of lymphocyte mediated cytotoxicity by perforin antisense oligonucleotides. EMBO J 9: 3815–3819

    Google Scholar 

  • Bakouche O, Ichinose Y, Hiecappel R, Fidler IS, Lachman LB (1988): Plasma membrane-associated tumor necrosis factor. A non-integral membrane protein possibly bound to its own receptor. J Immunol 140: 1142–1147

    Google Scholar 

  • Berke G, Rosen D (1988): Highly lytic in vivo primed cytolytic T lymphocytes devoid of lytic granules and BLT-esterase activity acquire these constituents in the presence of T cell growth factors upon blast transformation in vitro. J Immunol 141: 1429–1436

    Google Scholar 

  • Bleackley RC, Lobe CG, Duggan B, Ehrman N, Fregeau C, Meier M, Letellier M, Havele C, Shaw J, Paetkau V (1988): The isolation and characterization of a family of serine protease genes expressed in activated cytotoxic T lymphocytes. Immunol Rev 103: 5–19

    Article  Google Scholar 

  • Brunet JF, Denizot F, Suzan M. Haas W, Mencia-Huerta JM, Berke G, Luciani MF, Golstein P (1987): CTLA-1 and CTLA-3 serine esterase transcripts are detected mostly in cytotoxic T cells, but not only and not always. J Immunol 138: 4102–4105

    Google Scholar 

  • Dennert G, Anderson CG, Prochazka G (1987): High activity of Nx-benzylocarbonyl-L-lysine thiobenzyl ester serine esterase and cytolytic perforin in cloned cell lines is not demonstrable in in vivo-induced cytotoxic effector cells. Proc Natl Acad Sci USA 84: 5004–5008

    Article  Google Scholar 

  • Duke RC, Cohen JJ (1986): IL-2 addiction: Withdrawal of growth factor activates a suicide program in dependent T cells. Lymphokine Res 5: 289–293

    Google Scholar 

  • Duke RC, Chervenak R, Cohen JJ (1983): Endogenous endonuclease-induced DNA fragmentation: An early event in cell-mediated cytolysis. Proc Natl Acad Sci USA 80: 6361–6365

    Article  Google Scholar 

  • Duke RC, Persechini PM, Chang S, Liu C-C, Cohen JJ, Young JD-E (1989): Purified perforin induces target cell lysis but not DNA fragmentation. J Exp Med 170: 1451–1456

    Article  Google Scholar 

  • Erb P, Grogg D, Troxler M, Kennedy M, Fluri M (1990): CD4 T cell-mediated killing of MHC class II-positive antigen-presenting cells. I. Characterization of target cell recognition by in vivo or in vitro activated CD4+ killer T cells. J Immunol 144: 790–795

    Google Scholar 

  • Filippini A, Taffs RE, Sitkovsky MV (1990): Extracellular ATP in T-lymphocyte activation: Possible role in effector functions. Proc Natl Acad Sci USA 87: 8267–8271

    Article  Google Scholar 

  • Fong TA, Mosmann TR (1990): Alloreactive murine CD8+ cell clones secrete the Thl pattern of cytokines. J Immunol 144: 1744–1752

    Google Scholar 

  • Gajewski TF, Joyce J, Fitch FW (1989): Anti-proliferative effect of IFN-y in immune regulation. III. Differential selection of TH 1 and TH 2 murine helper T lymphocyte clones using recombinant IL-2 and recombinant IFN-y. J Immunol 143: 15–22

    Google Scholar 

  • Gajewski TF, Pinnas M, Wong T, Fitch FW (1991): Murine TH 1 and TH2 clones proliferate optimally in response to distinct antigen presenting cell populations. J Immunol 146: 1750–1758

    Google Scholar 

  • Gajewski TF, Schell SR, Fitch FW (1990): Evidence implicating utilization of different T cell receptor-associated signalling pathways by TH 1 and TH 2 clones. J Immunol 144: 4110–4120

    Google Scholar 

  • Garcia-Sanz JA, Plaetinck G, Velotti F, Masson D, Tschopp J, MacDonald HR, Nabholtz M (1987): Perforin is present only in normal activated Lyt2 + T lymphocytes and not in L3T4 + cells, but serine protease granzyme A is made by both subsets. EMBO J 6: 933–936

    Google Scholar 

  • Glasebrook AL, Fitch FW (1980): Alloreactive cloned T cell lines. I. Interactions between cloned amplified and cytolytic T cell lines. J Exp Med 151: 876–895

    Article  Google Scholar 

  • Glimcher LH, Sharrow SO, Paul WE (1983): Serologic and functional characterization of a panel of antigen-presenting cell lines expressing mutant I-A class II molecules. J Exp Med 158: 1573–1588

    Article  Google Scholar 

  • Gromkowski SH, Brown TC, Masson D, Tschopp J (1988): Lack of DNA degradation in target cells lysed by granules derived from cytolytic T lymphocytes. J Immunol 141: 774–778

    Google Scholar 

  • Hameed A, Olsen KJ, Lee M-K, Lichtenheld MG, Podack ER (1989): Cytolysis by Ca-permeable trans-membrane channels: Pore formation causes extensive DNA degradation and cell lysis. J Exp Med 767: 765–767

    Google Scholar 

  • Hengel H, Wagner H, Heeg K (1991): Triggering of CD8+ cytotoxic T lymphocytes via CD3-e differs from triggering via αββ T cell receptor. CD3-e-induced cytotoxicity occurs in the absence of protein kinase C and does not result in exocytosis of serine esterases. J Immunol 147: 1115–1120

    Google Scholar 

  • Henkart MP, Henkart PA (1982): Lymphocyte mediated cytolysis as a secretory phenomenon. Adv Exp Med Biol 146: 227–247

    Google Scholar 

  • Jenne DE, Tschopp J (1988): Granzymes, a family of serine proteases released from granules of cytolytic T lymphocytes upon T cell receptor stimulation. Immunol Rev 103: 53

    Article  Google Scholar 

  • Ju S-T (1991): Distinct pathways of CD4 and CD8 cells induce rapid target DNA fragmentation. J Immunol 146: 812–818

    Google Scholar 

  • Ju S-T, Ruddle NH, Strack P, Dorf ME, DeKruyff RH (1990): Expression of two distinct cytolytic mechanisms among murine CD4 subsets. J Immunol 144: 23–31

    Google Scholar 

  • Kim KJ, Kanellopoulos-Langevin C, Merwin RM, Sachs DH, Asofsky R (1979): Establishment and characterization of BALB/c lymphona lines with B cell properties. J Immunol 122: 549–554

    Google Scholar 

  • Klarnet JP, Kern DE, Dower SK, Matis LA, Cheever MA, Greenberg PD (1989): Helper-independent CD8+ cytotoxic T lymphocytes express IL-1 receptors and require IL-1 for secretion of IL-2. Jlmmunol 142: 2187–2191

    Google Scholar 

  • Lancki DW, Hsieh C-S, Fitch FW (1991a): Mechanisms of lysis by cytotoxic T lymphocyte clones: Lytic activity and gene expression in cloned antigen-specific CD4+ and CD8+ T lymphocytes. J Immunol 146: 3242–3249

    Google Scholar 

  • Lancki DW, Kaper BP, Fitch FW (1989): The requirements for triggering of lysis by cytolytic T lymphocyte clones. II. Cyclosporin A inhibits TCR-mediated exocytosis but only selectively inhibits TCR-mediated lytic activity by cloned CTL. J Immunol 142: 416–424

    Google Scholar 

  • Lancki DW, Ma DI, Havran WL, Fitch FW (1984): Cell surface structures involved in T cell activation. Immunol Rev 81: 65–94

    Article  Google Scholar 

  • Lancki DW, McKisic M, Hsieh C-S, Fitch FW (1991b): Mechanism of lysis by murine cytolytic and helper T cell clones. In: NK Cell Mediated Cytotoxicity: Receptors, Signalling and Mechanisms, Lotzovâ E, Herberman RB, eds. Boca Raton, FL: CRC Press

    Google Scholar 

  • Lanzavecchia A, Staerz UD (1987): Lysis of nonnucleated red blood cells by cytotoxic T lymphocytes. Eur J Immunol 17: 1073–1074

    Article  Google Scholar 

  • Leo O, Foo M, Henkart P, Perez P, Shinohara N, Segal D, Bluestone JA (1987): Activation of murine T lymphocytes with monoclonal antibody: Detection of Lyt2 + cells of an antigen not associated with the T cell receptor but involved in T cell activation. J Immunol 139: 1214–1222

    Google Scholar 

  • Leo O, Sachs DH, Samelson LE, Foo M, Quinones R, Gress R, Bluestone JA (1986): Identification of monoclonal antibodies specific for the T cell receptor complex by Fc receptor-mediated CTL lysis. J Immunol 137: 3874–3880

    Google Scholar 

  • Liu C-C, Joag SV, Kwon B, Young JD (1990): Induction of perforin and serine esterases in a murine cytotoxic T lymphocyte clone. J Immunol 144; 1196–1201

    Google Scholar 

  • Liu C-C, Steffan M, King F, Young JD-E (1987): Identification, isolation, and characterization of a novel cytotoxin in murine cytolytic lymphocytes. Cell 51: 393–403

    Article  Google Scholar 

  • Masson D, Tschopp J (1985): Isolation of a lytic, pore-forming protein (perforin) from cytolytic T-lymphocytes. J Biol Chem 260: 9069–9072

    Google Scholar 

  • McKisic MD, Sant AJ, Fitch FW (1991): Some cloned murine CD4+ T cells recognize H-2Ld Class I MHC determinants directly; other cloned CD4+ T cells recognize H-2Ld Class I MHC determinants in the context of Class II MHC molecules. J Immunol 147: 2868–2874

    Google Scholar 

  • Mercep M, Weissman AM, Frank SJ, Klausner RD, Ashwell JD (1989): Activation-driven programmed cell death and T cell receptor Crl expression. Science 246: 1162–1165

    Article  Google Scholar 

  • Millard PJ, Henkart MP, Reynolds CW, Henkart PA (1984): Purification and properties of cytoplasmic granules from cytotoxic granules from cytotoxic rat LGL tumors. J Immunol 132: 3197–3204

    Google Scholar 

  • Möller G, ed. (1988): Molecular mechanisms of T cell-mediated lysis. Immunol Rev 103: 1–211

    Google Scholar 

  • Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL (1986): Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136: 2348–2357

    Google Scholar 

  • Mueller C, Gershenfeld HK, Weissman IL (1988): Activation of CTL-specific genes during cell-mediated cytolysis in vivo: Expression of the HF gene analyzed by in situ hybridization. Immunol Rev 103; 73–85

    Article  Google Scholar 

  • Ostergaard HL, Kane KP, Mescher MF, Clark WR (1987): Cytotoxic T lymphocytes mediated lysis without release of serine esterase. Nature 330: 71–72

    Article  Google Scholar 

  • Pasternack MS, Eisen HN (1985): A novel serine esterase espressed by cytotoxic T lymphocytes. Nature 314: 743–745

    Article  Google Scholar 

  • Peters PJ, Borst J, Oorschot V, Fukuda M, Krähenbühl O, Tschopp, J, Slot JW, Geuze HJ (1991): Cytotoxic T lymphocyte granules are secretory lyosomes, containing both perforin and granzymes. J Exp Med 173: 1099–1109.

    Article  Google Scholar 

  • Podack ER, Konigsberg PJ (1984): Cytolytic T cell granules. Isolation, structural, biochemical, and functional characterization. J Exp Med 160: 695–710

    Article  Google Scholar 

  • Podack ER, Lowrey DM, Lichtenheld M, Olsen K, Aebischer T, Binder D, Rupp F, Hengartner H (1988): Structure, function, and expression of murine and human perforin 1 (P1). Immunol Rev 103: 203–211

    Article  Google Scholar 

  • Podack ER, Young JD-E, Cohn ZA (1985): Isolation and biochemical and functional characterization of perforin 1 from cytolytic T-cell granules. Proc Natl Acad Sci USA 82: 8629–8633

    Article  Google Scholar 

  • Ratner A, Clark WR (1991): Lack of target cell participation in cytotoxic T lymphocyte-mediated lysis. J Immunol 147: 55–59

    Google Scholar 

  • Russell JH (1983): Internal disintegration model of cytolytic lymphocyte-induced target damage. Immunol Rev 72: 97–118

    Article  Google Scholar 

  • Russell JH, Musil L, McCulley DE (1988): Loss of adhesion. A novel and distinct effect of the cytotoxic T lymphocyte-target interaction. J Immunol 140: 427–432

    Google Scholar 

  • Schmid DS, Tite JP, Ruddle NH (1986): DNA fragmentation: Manifestation of target cell destruction mediated by cytotoxic T-cell lines, lymphotoxin-secreting helper T-cell clones, and cell-free lymphotoxin-containing supernatant. Proc Natl Acad Sci USA 83: 1881–1885

    Article  Google Scholar 

  • Schumacher TNM, Heemels M-T, Neefjes JJ, Kast WM, Melief CJM, Ploegh HL (1990): Direct binding of peptide to empty MHC class I molecules on intact cells and in vitro. Cell 62: 563–567

    Article  Google Scholar 

  • Shiver JW, Henkart PA (1991): A noncytotoxic mast cell tumor line exhibits potent IgE-dependent cytotoxicity after transfection with the cytolysin/perforin gene. Cell 64: 1175–1181

    Article  Google Scholar 

  • Spits H, van Schooten W, Keizer H, van Seventer G, van de Rijn M, Terhorst C, De Vries JE (1986): Alloantigen recognition is preceded by nonspecific adhesion of cytotoxic T cells and target cells. Science 232: 403–405

    Article  Google Scholar 

  • Spits H, Yssel H, Leeuwenberg J, De Vries JE (1985): Antigen-specific cytotoxic T cell and antigen-specific proliferating T cell clones can be induced to cytolytic activity by monoclonal antibodies against T3. Eur J Immunol 15: 88–91

    Article  Google Scholar 

  • Staerz UD, Kanagawa O, Bevan MJ (1985): Hybrid antibodies can target sites for attack by T cells. Nature 314: 628–631

    Article  Google Scholar 

  • Strack P. Martin C, Saito S. DeKruyff RH, Ju ST (1990): Metabolic inhibitors distinguish cytolytic activity of CD4 and CD8 clones. Eur J Immunol 20: 179–184

    Article  Google Scholar 

  • Swain SL, Panfili PR (1979): Helper cells activated by allogeneic H-2K or H-2D differences have a Ly phenotype distinct from those responsive to I differences. J Immunol 122: 383–391

    Google Scholar 

  • Takayama H, Sitkovsky MV (1987): Antigen receptor-regulated exocytosis in cytoxic T lymphocytes. J Exp Med 166: 725–743

    Article  Google Scholar 

  • Takayama H, Trenn G, Sitkovsky MV (1987): A novel cytotoxic T lymphocyte activation assay: Optimized conditions for antigen receptor triggered granule enzyme secretion. J Immunol Methods 104: 183–185

    Article  Google Scholar 

  • Tite JP, Janeway CA, Jr (1984): Cloned helper T cells can kill B lymphoma cells in the presence of specific antigen: la restrication and cognate vs. non cognate interactions in cytolysis. Eur J Immunol 14: 878–886

    Article  Google Scholar 

  • Tite JP, Powell MB, Ruddle NH (1985): Protein-antigen specific Ia-restricted cytolytic T cells: Analysis of frequency, target cell susceptibility, and mechanism of cytolysis. J Immunol 135: 25–33

    Google Scholar 

  • 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: 72–74

    Article  Google Scholar 

  • Young JD (1989): Killing of target cells by lymphocytes: A mechanistic view. Physiol Rev 69: 250–314

    Google Scholar 

  • Young JD-E, Podack ER, Cohn ZA (1986): Properties of a purified pore-forming protein (perforin 1) isolated from H-2-restricted cytotoxic T cell granules. J Exp Med 164: 144–155.

    Article  Google Scholar 

Download references

Authors
  1. David W. Lancki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maureen McKisic
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Frank W. Fitch
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Laboratory of Immunology, Biochemistry and Immunopharmacology Unit, NIH-NIAID, 20892, Bethesda, Maryland, USA

    Michail V. Sitkovsky

  2. Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, 20892, Bethesda, Maryland, USA

    Pierre A. Henkart

Rights and permissions

Reprints and permissions

Copyright information

© 1993 Birkhäuser Boston

About this chapter

Cite this chapter

Lancki, D.W., McKisic, M., Fitch, F.W. (1993). Subpopulations of Cytotoxic T Lymphocytes with Different Cytotoxic Mechanisms. In: Sitkovsky, M.V., Henkart, P.A. (eds) Cytotoxic Cells: Recognition, Effector Function, Generation, and Methods. Birkhäuser Boston. https://doi.org/10.1007/978-1-4684-6814-4_15

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-6814-4_15

  • Publisher Name: Birkhäuser Boston

  • Print ISBN: 978-1-4684-6816-8

  • Online ISBN: 978-1-4684-6814-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation