Skip to main content
SpringerLink
Log in

Regulatory Effects of Cytokines on the Generation of CTL and LAK Cells

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

  • 130 Accesses

Abstract

It has long been recognized that the growth and differentiation of resting mature T lymphocytes into functional helper or cytolytic cells is dependent upon not only an antigenic stimulus but also soluble factors (Plate, 1976; Ryser et al., 1978). Consequently, recent attention has been focused upon the identification and further characterization of these soluble regulators. Following the description of interleukin-2 (IL-2) as a T-cell growth factor that can influence the generation of cytolytic T lymphocytes (CTL) (Gillis et al., 1978), it became apparent that several other cytokines exist which have similar activity. However, many of the early studies on T cell-active factors were clouded by the use of impure cytokine preparations and the possibility of indirect effects occurring in bulk lymphocyte cultures due to cytokine cascades. Thus, it was possible that a reputed T-cell growth factor or CTL induction factor was in fact affecting the secondary production of IL-2 or other T-cell growth factors, rather than itself directly stimulating T cells.

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

  • Alderson MR, Sassenfeld HM, Widmer MB (1990): Interleukin 7 enhances cytolytic T lymphocyte generation and induces lymphokine-activated killer cells from human peripheral blood. J Exp Med 172: 577–587

    Article  Google Scholar 

  • Aoki T, Kikuchi H, Miyatake S, Oda Y, Iwasaki K, Yamasaki T, Kinashi T, Honjo T (1989): Interleukin 5 enhances interleukin 2-mediated lymphokine-activated killer activity. J Exp Med 170: 583–588

    Article  Google Scholar 

  • Armitage RJ, Namen AE, Sassenfeld HM, Grabstein KH (1990): Regulation of human T-cell proliferation by interleukin 7. J Immunol 144: 938–941

    Google Scholar 

  • Borst J, van de Griend RJ, van Oostveen JW, Ang S, Melief CJ, Seidman JG, Bolhuis RLH (1987): A T-cell receptor y/CD3 complex found on cloned functional lymphocytes. Nature 325: 683–688

    Article  Google Scholar 

  • Chantry D, Turner M, Feldmann M (1989): Interleukin 7 (murine pre-B cell growth factor/lymphopoietin 1) stimulates thymocyte growth: Regulation by transforming growth factor beta. Eur J Immunol 19: 783–786

    Article  Google Scholar 

  • Chazen GD, Pereira GMB, LeGros G, Gillis S, Shevach EM (1989): Interleukin 7 is a T-cell growth factor. Proc Natl Acad Sci USA 86: 5923–5927

    Article  Google Scholar 

  • Chen L-K, Tourvieille B, Burns GF, Bach FH, MathieuMahul D, Sasportes M, Bensussan A (1986): Interferon: A cytotoxic T lymphocyte differentiation signal. Eur J Immunol 16: 767–770

    Article  Google Scholar 

  • Chen W-F, Zlotnick A (1991): IL-10: A novel cytotoxic T cell differentiation factor. J Immunol 147: 528–534

    Google Scholar 

  • Conlon PJ, Morrissey PJ, Nordan RP, Grabstein KH, Prickett KS, Reed SG, Goodwin R, Cosman D, Namen AE (1989): Murine thymocytes proliferate in direct response to interleukin-7. Blood 74: 1368–1373

    Google Scholar 

  • Ellis TM, McKenzie RS, Simms PE, Helfrich BA, Fisher RI (1989): Induction of human lymphokine-activated killer cells by IFN-a and IFN-y. J Immunol 143: 4282–4286

    Google Scholar 

  • Fanslow WC, Clifford KN, Park LS, Rubin AS, Voice RF, Beckmann MP, Widmer MB (1991): Regulation of alloreactivity in vivo by IL-4 and the soluble IL-4 receptor. J Immunol 147: 535–540

    Google Scholar 

  • Fanslow WC, Sims JE, Sassenfeld H, Morrissey PJ, Gillis S, Dower SK, Widmer MB (1990): Regulation of allo-reactivity in vivo by a soluble form of the interleukin-1 receptor. Science 248: 739–742

    Article  Google Scholar 

  • Fernandez-Botran R, Krammer PH, Diamantstein T, Uhr JW, Vitetta ES (1986): B cell-stimulatory factor 1 (BSF-1) promotes growth of helper T cell lines. J Exp Med 164: 580–593

    Article  Google Scholar 

  • Gillis S, Ferm MM, Ou W, Smith KA (1978): T cell growth factor: Parameters of production and a quantitative microassay for activity. J Immunol 120: 2027–2032

    Google Scholar 

  • Gillis S, Gillis AE, Henney CS (1981): Monoclonal antibody directed against interleukin-2. I. Inhibition of T lymphocyte mitogenesis and the in vitro differentiation of alloreactive cytolytic T cells. J Exp Med 154: 983–988

    Article  Google Scholar 

  • Grabstein KH, Park LS, Morrissey PJ, Sassenfeld H, Price V, Urdal DL, Widmer MB (1987): Regulation of murine T cell proliferation by B cell stimulatory factor-1. J Immunol 139: 1148–1153

    Google Scholar 

  • Grabstein KH, Namen AE, Shanebeck K, Voice RF, Reed SG, Widmer MB (1990): Regulation of T cell proliferation by IL-7. J Immunol 144: 3015–3020

    Google Scholar 

  • Grimm EA, Mazumder A, Zhang HZ, Rosenberg SA (1982): Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin-2-activated autologous human peripheral blood lymphocytes. J Exp Med 155: 1823–1841

    Article  Google Scholar 

  • Hickman CJ, Crim JA, Mostowski HS, Siegal JP (1990): Regulation of human cytotoxic T lymphocyte development by IL-7. J Immunol 145: 2415–2420

    Google Scholar 

  • Hu-Li J, Shevach EM, Mizuguchi J, Ohara J, Mosmann T, Paul WE (1987): B cell stimulatory factor 1 (interleukin 4) is a potent costimulant for normal resting T lymphocytes. J Exp Med 165: 157–172

    Article  Google Scholar 

  • Kaieda T, Okada M, Yoshimura N, Kishimoto S, Yamamura Y, Kishimoto T (1982): A human helper T cell clone secreting both killer helper factor(s) and T cell-replacing factor(s). J Immunol 129: 46–51

    Google Scholar 

  • Kawakami Y, Custer MC, Rosenberg SA, Lotze MT (1989): IL-4 regulates IL-2 induction of lymphokine-activated killer activity from human lymphocytes. J Immunol 142: 3452–3461

    Google Scholar 

  • Kern DE, Gillis S, Okada M, Henney CS (1981): The role of interleukin-2 (IL-2) in the differentiation of cytotoxic T cells: The effect of monoclonal anti-IL-2 antibody and absorption with IL-2 dependent T cell lines. J Immunol 127: 1323–1328

    Google Scholar 

  • Koide J, Rivas A, Engleman EG (1989): Natural killer (NK)-like cytotoxic activity of allospecific T cell receptor-7,6+ T cell clones. Distinct receptor-ligand interactions mediate NK-like and allospecific cytotoxicity. J Immunol 142: 4161–4168

    Google Scholar 

  • Lindqvist C, Nihlmark EL, Nordstrom T, Andersson LC (1991): Interleukin-4 downregulates the p70 chain of the IL-2 receptor on peripheral blood mononuclear cells. Cell Immunol 136: 62–68

    Article  Google Scholar 

  • Londei M, Verhoef A, Hawrylowicz C, Groves J, De Berardinis P, Feldmann M (1990): Interleukin 7 is a growth factor for mature human T cells. Eur J Immunol 20: 425–428

    Article  Google Scholar 

  • Lotze MT, Grimm EA, Mazumder A, Strausser JL, Rosenberg SA (1981): Lysis of fresh and cultured autologous tumor by human lymphocytes cultured in T cell growth factor. Cancer Res 41: 4420–4425

    Google Scholar 

  • Luger TA, Krutmann J, Kirnbauer R, Urbanski A, Schwarz T, Klappacher G, Kock A, Micksche M, Malejczyk J, Schauer E, May LT, Sehgal PB (1989): IFN-Ăź2/IL-6 augments the activity of human natural killer cells. J Immunol 143: 1206–1209

    Google Scholar 

  • Lynch DH, Miller RE (1990): Induction of murine lymphokine-activated killer cells by recombinant IL-7. J Immunol 145: 1983–1990

    Google Scholar 

  • MacDonald HR, Cerottini J-C, Ryser J-E, Maryanski JL, Taswell C, Widmer MB, Brunner KT (1980): Quantitation and cloning of cytolytic T lymphocytes and their precursors. Immunol Rev 51: 93–123

    Article  Google Scholar 

  • Mannel DN, Falk W, Droge W (1983): Induction of cytotoxic T cell function requires sequential action of three different lymphokines. J Immunol 130: 2508–2510

    Google Scholar 

  • Maraskovsky E, Chen W-F, Shortman K (1989): IL-2 and IFN-y are two necessary lymphokines in the development of cytolytic T cells. J Immunol 143: 1210–1214

    Google Scholar 

  • Moingeon P, Jitsukawa S, Faure F, Troalen F, Triebel F, Graziani M, Forestier F, Bellet D, Bohuon C, Hercend T (1987): A y-chain complex forms a functional receptor on cloned human lymphocytes with natural killer-like activity. Nature 325: 723–726

    Article  Google Scholar 

  • Morrissey Pi, Goodwin RG, Nordan RP, Anderson D, Grabstein KH, Cosman D, Sims J, Lupton S, Acres B, Reed SG, Mochizuki D, Eisenman J, Conlon PJ, Namen AE (1989): Recombinant interleukin 7, pre-B cell growth factor, has costimulatory activity on purified mature T cells. J Exp Med 169: 707–716

    Article  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 

  • MulĂ© JJ, Smith CA, Rosenberg SA (1987): Interleukin 4 (B cell stimulatory factor 1) can mediate the induction of lymphokine-activated killer cell activity directed against fresh tumor cells. J Exp Med 166: 792–797

    Article  Google Scholar 

  • Nagler A, Lanier LL, Phillips JH (1988): The effects of IL-4 on human natural killer cells. A potent regulator of IL-2 activation and proliferation. J Immunol 141: 2349–2351

    Google Scholar 

  • Namen AE, Lupton S, Hjerrild K, Wignall J, Mochizuki DY, Schmierer A, Mosley B, March CJ, Urdal D, Gillis S, Cosman D, Goodwin RG (1988): Stimulation of B-cell progenitors by cloned murine interleukin-7. Nature 6173: 571–573

    Article  Google Scholar 

  • Noma Y, Sideras P, Naito T, Bergstedt-Lindquist S, Azuma C, Severinson E, Tanabe T, Kinashi T, Matsuda F, Yaoita Y, Honjo T (1986): Cloning of cDNA encoding the murine IgG l induction factor by a novel strategy using SP6 promoter. Nature 319: 640–646

    Article  Google Scholar 

  • Okada M, Kitahara M, Kishimoto S, Matsuda T, Hirano T, Kishimoto T (1988): IL-6/BSF-2 functions as a killer helper factor in the in vitro induction of cytotoxic T cells. J Immunol 141: 1543–1549

    Google Scholar 

  • Okazaki H, Ito M, Sudo T, Hattori M, Kano S, Katsura Y, Minato N (1989): IL-7 promotes thymocyte proliferation and maintains immunocompetent thymocytes bearing aĂź or yS T-cell receptors in vitro: Synergism with IL-2 J Immunol 143: 2917–2922

    Google Scholar 

  • Paliard X, Yssel H, Blanchard D, Waitz JA, de Vries JE, Spits H (1989): Antigen-specific and MHC nonrestricted cytotoxicity of T cell receptor aĂź and;S+ human T cell clones isolated in IL-4. J Immunol 143: 452–457

    Google Scholar 

  • Paul WE, Ohara J (1987): B-cell stimulatory factor-I/ interleukin 4. Annu Rev Immunol 5: 429–459

    Article  Google Scholar 

  • Pfeifer JD, McKenzie DT, Swain SL, Dutton RW (1987): B cell stimulatory factor 1 (interleukin-4) is sufficient for the proliferation and differentiation of lectinstimulated cytolytic T lymphocyte precursors. J Exp Med 166: 1464–1470

    Article  Google Scholar 

  • Plate JMD (1976): Soluble factors substitute for T-T-cell collaboration in generation of T-killer lymphocytes. Nature 260: 329–331

    Article  Google Scholar 

  • Raulet DH, Bevan MJ (1982): A differentiation factor required for the expression of cytotoxic T-cell function. Nature 296: 754–757

    Article  Google Scholar 

  • Rosenberg SA, Lotze MT (1986): Cancer immunotherapy using interleukin-2 and interleukin-2-activated lymphocytes. Annu Rev Immunol 4: 681–709

    Article  Google Scholar 

  • Rosenberg SA, Lotze MT, Yang JC, Aebersold PM, Linehan WM, Seipp CA, White DE (1989): Experience with the use of high-dose interleukin-2 in the treatment of 652 cancer patients. Ann Surg 210: 474–484

    Article  Google Scholar 

  • Rosenberg SA, Speiss P, Lafreniere R (1986): A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science 233: 1318–1321

    Article  Google Scholar 

  • Ryser J-E, Cerottini JC, Brunner KT (1978): Generation of cytolytic T lymphocytes in vitro. IX. Induction of secondary CTL responses in primary long-term MLC by supernatants from secondary MLC. J Immunol 120: 370–377

    Google Scholar 

  • Schorle H, Holtschke T, Hunig T, Schimpl A, Horak I (1991): Development and function of T cells in mice rendered interleukin-2 deficient by gene targeting. Nature 352: 621–624

    Article  Google Scholar 

  • Simon MM, Hochgeschwender U, Brugger U, Landolfo S (1986): Monoclonal antibodies to interferon-y inhibit interleukin 2-dependent induction of growth and maturation in lectin/antigen-reactive cytolytic T lymphocyte precursors. J Immunol 136: 2755–2762

    Google Scholar 

  • Spits H, Yssel H, Paliard X, Kastelein R, Figdor C, de Vries JE (1988): IL-4 inhibits IL-2-mediated induction of human lymphokine-activated killer cells, but not the generation of antigen-specific cytotoxic T lymphocytes in mixed leukocyte cultures. J Immunol 141: 29–36

    Google Scholar 

  • Stotter H, Custer MC, Bolton, ES, Guedez L, Lotze MT (1991): IL-7 induces human lymphokine-activated killer cell activity and is regulated by IL-4. J Immunol 146: 150–155

    Google Scholar 

  • Swisher SG, Economou JS, Carmack Holmes E, Golub SH (1990): TNF-a and IFN-y reverse IL-4 inhibition of lymphokine-activated killer cell function. Cell Immunol 128: 450–461

    Article  Google Scholar 

  • Takai Y, Herrmann SH, Greenstein JL, Spitainy GL, Burakoff SJ (1986): Requirement for three distinct lymphokines for the induction of cytotoxic T lymphocytes from thymocytes. J Immunol 137: 3494–3500

    Google Scholar 

  • Takai Y, Wong GG, Clark SC, Burakoff SJ, Herrmann SH (1988): B cell stimulatory factor-2 is involved in the differentiation of cytotoxic T lymphocytes. J Immunol 140: 508–512

    Google Scholar 

  • Wagner H, Hardt C, Rouse BT, Rollinghoff M, Scheurich P, Pfizenmaier K (1982): Dissection of the proliferative and differentiative signals controlling murine cytotoxic T lymphocyte responses. J Exp Med 155: 1876–1881

    Article  Google Scholar 

  • Watson JD, Morrissey PJ, Namen AE, Conlon PJ, Widmer MB (1989): Effect of IL-7 on the growth of fetal thymocytes in culture. J Immunol 143: 1215–1222

    Google Scholar 

  • Widmer MB, Grabstein KH (1987): Regulation of cytolytic T-lymphocyte generation by B-cell stimulatory factor. Nature 326: 795–798

    Article  Google Scholar 

  • Widmer MB, Acres RB, Sassenfeld HM, Grabstein KH (1987): Regulation of cytolytic cell populations from human peripheral blood by B cell stimulatory factor 1 (interleukin 4). J Exp Med 166: 1447–1455

    Article  Google Scholar 

  • Widmer MB, Morrissey PJ, Namen AE, Voice RF, Watson JD (1990): Interleukin 7 stimulates growth of fetal thymic precursors of cytolytic cells: Induction of effector function by interleukin 2 and inhibition by interleukin 4. Int Immunol 2: 1055–1061

    Article  Google Scholar 

  • Wolf SF, Temple PA, Kobayashi M, Young D, Dicig M, Lowe L, Dzialo R, Fitz L, Ferenz C, Hewick RM, Kelleher K, Herrmann SH, Clark SC, Azzoni L, Chan SH, Trinchieri G, Perussia B (1991): Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells. J Immunol 146: 3074–3081

    Google Scholar 

Download references

Authors
  1. Mark R. Alderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael B. Widmer
    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

Alderson, M.R., Widmer, M.B. (1993). Regulatory Effects of Cytokines on the Generation of CTL and LAK Cells. 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_11

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-6814-4_11

  • 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