Skip to main content
PMC home page
Cancer Immunology, Immunotherapy : CII logoLink to Cancer Immunology, Immunotherapy : CII
. 1989 Jun;29(2):125–132. doi: 10.1007/BF00199287

Auto-tumor lysis by blood lymphocytes in vitro

Strongly activated lymphocytes lack selectivity

F Vánky 1,✉, E Klein 1
PMCID: PMC11038039  PMID: 2470505

Abstract

Selectivity of the lysis of the tumor cells by autologous blood lymphocytes and its various subsets was investigated by means of the cold target competition assay. The effectors were autologous lymphocytes passed through a nylon-wool column (unfractionated: U) and their low-and high-density subsets, either without or after activation. The lymphocytes were activated (a) in autologous mixed lymphocyte tumor cell culture in autologous (MLTC), (b) in mixed lymphocyte culture (MLC), without and with interleukin-2, for 6 days, or (c) by phytohaemagglutinin for 3 days. Autologous-lymphocyte-mediated cytotoxicity (auto-tumor lysis: ALC) by the unfractionated, unmanipulated blood lymphocyte (U) population, its high-density fraction and those induced for auto-tumor lysis in the MLTC is regularly weak and affects only the autologous tumor cells. Their ALC function was inhibited only by the target identical unlabelled cells while the effect of separated low-density lymphocytes was inhibited also by allogeneic tumor cells.

The cold-target competition assay indicated that several subsets with different specificities exist simultaneously in the effector populations activated in MLC, because the various targets did not cross-compete or did so only partially. Whenever interleukin-2 was added, at the start of the mixed cultures (MLTC or MLC), the lytic effects were no longer selective. Phytohaemagglutinin-activated effectors lysed several targets. These targets were inhibitory in a criss-cross fashion. Generally, populations showing auto-tumor selectivity had weak lytic effects, while the strongly activated effectors, with strong cytotoxic function, were not selective.

Keywords: Mixed Culture, Blood Lymphocyte, Effector Population, Autologous Blood, Autologous Tumor

References

  • 1.Balsari A, Fossati G, Taramelli D, Tona G, Delia D, Giardini R, Parmiani G. Allostimulation of patients lymphocytes generates both T and NK-like cells cytotoxic for autologous melanoma. Br J Cancer. 1985;52:73. doi: 10.1038/bjc.1985.151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Galili U, Galili N, Vánky F, Klein E. Natural species restricted attachment of human and murine T lymphocytes to various cells. Proc Natl Acad Sci USA. 1978;75:2396. doi: 10.1073/pnas.75.5.2396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Grimm EA, Mazumder A, Zhang HZ, Rosenberg SA. Lymphokine activated killer cell phenomenon. Lysis of natural killer cell resistant fresh solid tumor cells by interleukin-2 activated autologous human periferal blood lymphocytes. J Exp Med. 1982;155:1823. doi: 10.1084/jem.155.6.1823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Heo DS, Whiteside TL, Kanbour A, Herberman RB. Lymphocytes infiltrating human tumors. I. Role of Leu-19 (NKH1)-positive recombinant IL-2-activated cultures of lymphocytes infiltrating human ovarian tumors. J Immunol. 1988;140:4042. [PubMed] [Google Scholar]
  • 5.Hynes RO. Integrins. A family of cell surface receptors. Cell. 1987;48:159. doi: 10.1016/0092-8674(87)90233-9. [DOI] [PubMed] [Google Scholar]
  • 6.Itoh K, Tilden AB, Balch CM. Lysis of human solid tumor cells by lymphokine-activated natural killer cells. J Immunol. 1986;136:1910. [PubMed] [Google Scholar]
  • 7.Klein E. Lymphocyte mediated lysis of tumor cells in vitro, antigen restricted colnal and unrestricted polyclonal effects. Springer Semin Immunopathol. 1982;5:147. doi: 10.1007/BF00199793. [DOI] [PubMed] [Google Scholar]
  • 8.Klein E, Vánky F. Natural and activated cytotoxic lymphocytes which act on autologous and allogeneic tumor cells. Cancer Immunol Immunother. 1981;11:183. [Google Scholar]
  • 9.Klein E, Vánky F, Masucci MG, Bejarano MT. Experimental and clinical data for the role of NK cells in immunosurveillance. Behring Inst Mitt. 1984;74:140. [PubMed] [Google Scholar]
  • 10.Klein E, Vánky F, Stuber G (1988) Lysis of autologous tumor cells by blood lymphocytes in vitro requires MHC class I antigen expression. Springer Semin Immunopath (in press)
  • 11.Landazuri OM, Herberman RB. Specificity of cellular immune reactivity to virus induced tumors. Nature. 1972;238:18. doi: 10.1038/newbio238018a0. [DOI] [PubMed] [Google Scholar]
  • 12.Lanier LL, Cwirla S, Ferderspiel N, Philips JH. Human natural killer cells isolated from periferal blood do not rearrange T-cell receptor beta chain genes. J Exp Med. 1986;163:209. doi: 10.1084/jem.163.1.209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.LeFor AT, Eisenthal A, Rosenberg SA. Heterogenicity of lymphokine activated killer cells induced by IL-2. Separate lymphoid subpopulations lyse tumor, allogeneic blasts, and modified syngeneic blasts. J Immunol. 1988;140:4062. [PubMed] [Google Scholar]
  • 14.Leshem B, Gotsman B, Kedar E. In vitro elicitation of cytotoxic response against a nonimmunogenic murine tumor by allosensitisation. Cancer Immunol Immunother. 1984;17:117. doi: 10.1007/BF00200047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Longley RE, Good RA. Leukemia prevention and long-term survival of AKR mice transplanted with MHC-matched or MHC-mismatched bone marrow. Cell Immunol. 1986;101:476. doi: 10.1016/0008-8749(86)90159-0. [DOI] [PubMed] [Google Scholar]
  • 16.Masucci MG, Klein E, Argov S. Disappearance of NK effect after explantation of lymphocytes and generation of similar non-specific cytotoxicity correlated to the level of blastogenesis in activated cultures. J Immunol. 1980;124:2458. [PubMed] [Google Scholar]
  • 17.Mazumder A, Grimm EA, Rosenberg SA. Lysis of fresh human solid tumor cells by autologous lymphocytes activated in vitro by allosensitization. Cancer Immunol Immunother. 1983;15:1. doi: 10.1007/BF00199454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Paciucci PA, Macphail S, Zarling JM, Bach FH. Lysis of syngeneic solid tumor cells by alloantigen stimulated mouse T and non-T cells. J Immunol. 1980;124:370. [PubMed] [Google Scholar]
  • 19.Santoli D, Koprowski H. Mechanism of activation of human natural killer cells against tumor and virus-infected cells. Immunol Rev. 1979;44:126. doi: 10.1111/j.1600-065x.1979.tb00269.x. [DOI] [PubMed] [Google Scholar]
  • 20.Schlossman SF. Antigen recognition: the specificity of T-cells involved in the cellular immune response. Transplant Rev. 1972;10:97. doi: 10.1111/j.1600-065x.1972.tb01540.x. [DOI] [PubMed] [Google Scholar]
  • 21.Seely JK, Golub SH. Studies on cytotoxicity generated in human mixed lymphocyte cultures. I. Time course and target spectrum of several distinct concomitant cytotoxic activities. J Immunol. 1978;120:1415. [PubMed] [Google Scholar]
  • 22.Strausser JL, Mazumder A, Grimm EA, Lotze MT, Rosenberg SA. Lysis of human solid tumors by autologous cells sensitized in vitro to alloantigens. J Immunol. 1981;127:266. [PubMed] [Google Scholar]
  • 23.Timonen T, Saksela E, Ranki A, Häyry P. Fractionation, morphological and functional characterization of effector cells responsible for human natural killer activity against cell-line targets. Cell Immunol. 1979;48:133. doi: 10.1016/0008-8749(79)90106-0. [DOI] [PubMed] [Google Scholar]
  • 24.Thorsby E, Berle E, Nousianen H. HLA-D region molecules restrict proliferative T-cell responses to antigen. Immunol Rev. 1982;66:39. doi: 10.1111/j.1600-065x.1982.tb00433.x. [DOI] [PubMed] [Google Scholar]
  • 25.Truitt RL, Shih CC-Y, Lefever AV. Manipulation of graft versus host disease for a graft versus leukemia effect after allogeneic bone marrow transplantation in AKR mice with spontaneous leukemia/lymphoma. Transplantation. 1986;41:301. doi: 10.1097/00007890-198603000-00005. [DOI] [PubMed] [Google Scholar]
  • 26.Vánky F, Vose BM, Fopp M, Klein E. Human tumorlymphocyte interaction in vitro. VI. Specificity of primary and secondary autologous lymphocyte mediated cytotoxicity. J Natl Cancer Inst. 1979;62:1407. [PubMed] [Google Scholar]
  • 27.Vánky F, Argov S, Einhorn S, Klein E. Role of alloantigens in natural killing. Allogeneic but not autologous tumor biopsy cells are sensitive for interferon-induced cytotoxicity of human blood lymphocytes. J Exp Med. 1980;151:1151. doi: 10.1084/jem.151.5.1151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Vánky F, Argov S, Klein E. Tumor biopsy cells participating in systems in which cytotoxicity of lymphocytes is generated. Autologous and allogeneic studies. Int J Cancer. 1981;27:273. doi: 10.1002/ijc.2910270304. [DOI] [PubMed] [Google Scholar]
  • 29.Vánky F, Masucci MG, Bajarano MT, Klein E. Lysis of tumor biopsy cells by blood lymphocytes of various densities. Autologous and allogeneic studies. Int J Cancer. 1984;33:185. doi: 10.1002/ijc.2910330206. [DOI] [PubMed] [Google Scholar]
  • 30.Vánky F, Klein E, Willems J, Böök K, Ivert T, Péterffy A, Nilsonne U, Kreicbergs A, Aparisi T. Lysis of autologous tumor cells tested at the time of surgery. Correlation with the postsurgical clinical course. Cancer Immunol Immunother. 1986;21:69. doi: 10.1007/BF00199380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Vánky F, Klein E, Willems J, Böök K, Ivert T, Péterffy A. Recognition of autologous tumor cells by blood lymphocytes in patients with lung cancer. In: Byers VS, Baldwin RW, editors. Immunology of malignant diseases. Lancaster: MTP Press Ltd; 1987. pp. 105–128. [Google Scholar]
  • 32.Vánky F, Roberts T, Klein E, Willems J. Auto-tumor immunity in patients with solid tumors. Participation of CD3 complex and MHC class I antigens in the lytic interaction. Immunol Lett. 1987;16:21. doi: 10.1016/0165-2478(87)90055-1. [DOI] [PubMed] [Google Scholar]
  • 33.Vánky F, Stuber G, Willems J, Sjöwall K, Larsson B, Böök K, Ivert T, Péterffy A, Klein E. Importance of MHC antigen expression on solid tumors in the in vitro interaction with autologous blood lymphocytes. Cancer Immunol Immunother. 1988;27:213. doi: 10.1007/BF00205442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Vánky F, Stuber G, Rotstein S, Klein E. Auto-tumor recognition following in vitro induction of MHC antigen expression on solid human tumors: stimulation of lymphocytes and generation of cytotoxicity against the original MHC antigen negative tumor cells. Cancer Immunol Immunother. 1989;28:17. doi: 10.1007/BF00205795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Vose BM, White W. Tumor reactive lymphocytes stimulated in mixed lymphocyte and tumor culture. Clonal analysis of effector cells in cytotoxic and proliferative assays. Cancer Immunol Immunother. 1983;15:227. doi: 10.1007/BF00199170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Vose BM, Vánky F, Fopp M, Klein E. Restricted autologous lymphocytotoxicity in lung neoplasia. Br J Cancer. 1978;38:372. doi: 10.1038/bjc.1978.217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Zinkernagel R, Doherty P. MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificities, function and responsiveness. Adv Immunol. 1979;27:51. doi: 10.1016/s0065-2776(08)60262-x. [DOI] [PubMed] [Google Scholar]

Articles from Cancer Immunology, Immunotherapy : CII are provided here courtesy of Springer

RESOURCES