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. 1997 Oct;45(1):29–36. doi: 10.1007/s002620050397

Augmentation of impaired tumoricidal function in alveolar macrophages from lung cancer patients by cocultivation with allogeneic, but not autologous lymphocytes

Kalliopi P Siziopikou 1,2, Mi-Chung Ahn 2, Larry Casey 3, Mike Silver 3, Jules E Harris 1,2, Donald P Braun 1,2,✉
PMCID: PMC11037803  PMID: 9353424

Abstract

It has been reported that the in vitro development of tumoricidal function in alveolar macrophages from lung cancer patients is reduced significantly when compared to that in peripheral blood monocytes from the same patients or alveolar macrophages from control patients. In the present investigation, a method for potentiating the development of tumoricidal function in alveolar macrophages from lung cancer patients is described. This method, which relies on priming the macrophages with purified, allogeneic peripheral blood lymphocytes from normal donors, could not be demonstrated when autologous lymphocytes from lung cancer patients were used in the priming coculture. The augmentation of tumoricidal function appears to be mediated by one or more soluble factors, since supernatants from cocultures of alveolar macrophages and allogeneic peripheral blood lymphocytes could enhance the cytotoxic function of freshly obtained alveolar macrophages. Furthermore, it appears that NK cells are necessary for this effect, since depletion of CD56+/CD57+ cells from allogeneic lymphocytes eliminated their capacity to enhance alveolar macrophage cytotoxic function. The augmentation of cytotoxic function elicited in alveolar macrophages by this method was not associated with changes in the secretion of tumor necrosis factor α, or interleukin 1β.

Key words: Alveolar macrophages, Tumoricidal activity, PBL, Lung cancer

References

  • 1.Anderson TM, Ibayashi Y, Holmes EC, Golub SH. Modification of natural killer activity of lymphocytes infiltrating human lung cancers. Cancer Immunol Immunother. 1987;25:65–65. doi: 10.1007/BF00199303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Bandyopadhyay S, Perussia B, Trinchieri G. Requirement for HLA-DR+ accessory cells in natural killing of cytomegalovirus infected fibroblasts. J Exp Med. 1986;104:180–180. doi: 10.1084/jem.164.1.180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Blue ML, Daley JF, Levine H, Branton KR, Schlossman SF. Regulation of CD4 and CD8 surface expression on human thymocyte subpopulations by triggering through CD2 and CD3 T cell receptors. J Immunol. 1989;142:374–374. [PubMed] [Google Scholar]
  • 4.Braun DP, Harris JE. Relationship of leukocyte numbers, immunoregulatory cell function, and phytohemagglutinin responsiveness in cancer patients. J Natl Cancer Inst. 1981;67:809–809. [PubMed] [Google Scholar]
  • 5.Braun DP, Cobleigh MA, Harris JE. Multiple concurrent immunoregulatory defects in cancer patients with depressed PHA-induced lymphocyte DNA synthesis. Clin Immunol Immunopathol. 1980;17:89–89. doi: 10.1016/0090-1229(80)90076-8. [DOI] [PubMed] [Google Scholar]
  • 6.Dang NH, Torimoto Y, Deusch K, Schlossman SF, Morimoto C. Comitogenic effect of solid phase immobilized anti-1F7 on human CD4 T cell activation via CD3 and CD2 pathways. J Immunol. 1990;144:4092–4092. [PubMed] [Google Scholar]
  • 7.DeFrutas E, Chernut R, Grey H, Chiller J. Macrophage dependent activation of antigen specific T cells requires antigen and a soluble monokine. J Immunol. 1983;131:23–23. [PubMed] [Google Scholar]
  • 8.Dührsen V, Uppenhamp M, Uppenkamp I. Chronic T cell leukemia with unusual cellular characteristics in ataxia telangiectasia. Blood. 1986;68:577–577. [PubMed] [Google Scholar]
  • 9.Duggan DB. Immunology and inflammation. Basic mechanisms and clinical consequences. New York: McGraw Hill; 1994. Cytokines: intercellular messengers of proliferation and function; pp. 185–207. [Google Scholar]
  • 10.Engleman EG, Benike CJ, Hoppe RT, Kaplan HS, Berberich FR. Autologous mixed lymphocyte reactions in patients with Hodgkin’s disease. J Clin Invest. 1980;66:149–149. doi: 10.1172/JCI109828. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Erb P, Feldmann M. The role of macrophages in the generation of T helper cells. I. The requirement for macrophages in helper cell induction and characteristics of the macrophage-T cell interaction. Cell Immunol. 1979;19:356–356. doi: 10.1016/0008-8749(75)90217-8. [DOI] [PubMed] [Google Scholar]
  • 12.Faure F, Jitsukawa S, Meurer SC, Bohuon C, Triebel F, Hercend T. Identification of a CD2−/CD3+ T cell receptor-γ+ peripheral blood lymphocyte subpopulation. J Immunol. 1988;140:2128–2128. [PubMed] [Google Scholar]
  • 13.Gangemi JD, Olsen GN, Fechtez C, Hightower JA, Bauguess CT, Krech L. Phagocytic activity of alveolar macrophages in patients with bronchogenic carcinoma. Cancer Immunol Immunother. 1985;20:158–158. doi: 10.1007/BF00205683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Gomez J, Pohajdak B, O’Neill S, Wilkins J, Greenberg AH. Activation of rat and human alveolar macrophage intracellular microbicidal activity by a preformed LGL cytokine. J Immunol. 1985;135:1194–1194. [PubMed] [Google Scholar]
  • 15.Gottleib A, Fu S, Yu D, Wang C, Halper J, Kunkel H. The nature of the stimulatory cells in human allogeneic and autologous MLC reactions; role of isolated IgM bearing B cells. J Immunol. 1979;123:1497–1497. [PubMed] [Google Scholar]
  • 16.Hoover DL, Meltzer MS. Lymphokines as monocyte activators. In: Zembala M, Ascherson GL, editors. Human monocytes. London: Academic Press; 1989. pp. 151–151. [Google Scholar]
  • 17.Hünig T, Tiefenthaler G, Meyer zum Büschenfelde KH, Meuer SC. Alternative pathway activation of T cells by binding of CD2 to its cell surface ligand. Nature. 1987;326:298–298. doi: 10.1038/326298a0. [DOI] [PubMed] [Google Scholar]
  • 18.Kabelitz D, Conradt P. Identification of CD2−/CD3+ T cells in fetal human tissue. J Exp Med. 1988;168:1941–1941. doi: 10.1084/jem.168.5.1941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Kan-Mitchell J, Hengst JCD, Kempf RA, Rothbart RK, Simons SM, Brooker AS, Kortes VL, Mitchell MS. Cytotoxic activity of human pulmonary alveolar macrophages. Cancer Res. 1985;45:453–453. [PubMed] [Google Scholar]
  • 20.Kasahara T, Djeu JD, Dougherty SF, Oppenheim JJ. Capacity of human large granular lymphocytes (LGL) to produce multiple lymphokines: interleukin 2, interferon, and colony stimulating factor. J Immunol. 1983;131:2379–2379. [PubMed] [Google Scholar]
  • 21.Katz P, Mitchell SR, Cupps TR, Evans M, Whalen G (1989) Natural killer cells enhance the early events in B cell activation. In: Ades EW, Lopez C (eds) Natural killer cells and host defense. 5th International Natural Killer Cell Workshop. Karger, Basel, p 59
  • 22.Krammer G, Unanue E. Accessory cell requirements in the proliferative response to T lymphocytes to hemocyanin. Clin Immunol Immunopathol. 1982;129:1360–1360. doi: 10.1016/0090-1229(80)90055-0. [DOI] [PubMed] [Google Scholar]
  • 23.Krensky AM, Lanier LL, Engleman EG. Lymphocyte subsets and surface molecules in man. Clin Immunol Res. 1985;4:95–95. [PubMed] [Google Scholar]
  • 24.Kuda T, Yasumoto K, Yano T, Nukahashi H, Sugimashi K, Nomoto K. Role of antitumor activity of alveolar macrophages in lung cancer patients. Cancer Res. 1987;47:2199–2199. [PubMed] [Google Scholar]
  • 25.Lanier LL, Le AM, Civin CI, Loken MR, Phillips JH. The relationship of CD16 (Leu11) and Leu19 (NKH-1) antigen expression on human peripheral blood NK cells and cytotoxic T lymphocytes. J Immunol. 1986;136:4480–4480. [PubMed] [Google Scholar]
  • 26.Lemarble P, Hoidal J, Vesella R, Rinehart J. Human pulmonary macrophage tumor cell cytotoxicity. Blood. 1980;55:612–612. [PubMed] [Google Scholar]
  • 27.Mann D, Abelson L. Monocyte function in mixed lymphocyte reactions. Cell Immunol. 1980;56:357–357. doi: 10.1016/0008-8749(80)90111-2. [DOI] [PubMed] [Google Scholar]
  • 28.Matera L, Avanzi G, Cesano A, Bellone G, Malavasi F, Pegoraro L (1989) Characterization of hemopoietic regulatory factors released by unstimulated LGL. In: Ades EW, Lopez C (eds) Natural killer cells and host defense. 5th International Natural Killer Cell Workshop. Karger, Basel, p 92
  • 29.Michael A, Hackett J, Kumar V, Yuan D (1989) Interaction of B lymphocytes and NK cells. 1989. In: Ades EW, Lopez C (eds) Natural killer cells and host defense. 5th International Natural Killer Cell Workshop. Karger, Basel, p 75
  • 30.Moy MP, Holmes EC, Golub SH. Depression of NK cytotoxic activity in lymphocytes infiltrating human pulmonary tumors. Cancer Res. 1985;45:57–57. [PubMed] [Google Scholar]
  • 31.Naito K, Komatsubara S, Kawai J, Morl K, Muramatusu S. Role of macrophages as modulators but not as stimulators in primary mixed leukocyte reactions. Cell Immunol. 1984;88:361–361. doi: 10.1016/0008-8749(84)90169-2. [DOI] [PubMed] [Google Scholar]
  • 32.Nathan CF, Karnovsky NL, David JR. Alterations of macrophage functions by mediators from lymphocytes. J Exp Med. 1971;133:1356–1356. doi: 10.1084/jem.133.6.1356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Ohlén C, Kling G, Höglung P, Hansson M, Scangos G, Bieberich C, Jay G, Kärre K. Prevention of allogeneic bone marrow graft rejection by H-2 transgene donor mice. Science. 1989;246:666–666. doi: 10.1126/science.2814488. [DOI] [PubMed] [Google Scholar]
  • 34.Paya CV, Kenmotsu N, Leibson PJ (1989) Tumor necrosis factor and lymphotoxin secretion by human natural killer cells leads to antiviral cytotoxicity. In: Ades EW, Lopez C (eds) Natural killer cells and host defense. 5th International Natural Killer Cell Workshop. Karger, Basel, p 120 [PubMed]
  • 35.Pitchenic AE, Guffee J, Stein-Steilein J. Lung NK and IL 2 activity in lung cancer: a pulmonary compartement of augmented NK activity occurs in patients with bronchogenic carcinoma. Am Rev Respir Dis. 1987;136:1327–1327. doi: 10.1164/ajrccm/136.6.1327. [DOI] [PubMed] [Google Scholar]
  • 36.Rhodes J, Plowman P, Bishop M, Lipscomb D. Human macrophage function in cancer: systemic and local changes detected by an assay for FcR expression. J Natl Cancer Inst. 1981;66:423–423. [PubMed] [Google Scholar]
  • 37.Roussel E, Greenberg AH (1989) A heat stable peptide contained in large granular lymphocyte granules that activate macrophages. In: Ades EW, Lopez C (eds) Natural killer cells and host defense. 5th International Natural Killer Cell Workshop. Karger, Basel, p 146
  • 38.Scala G, Allaneva P, Djeu JD, Kasahara T, Ortaldo JR, Herberman RB, Oppenheim JJ. Human large granular lymphocytes are potent producers of interleukin 1. Nature. 1984;309:56–56. doi: 10.1038/309056a0. [DOI] [PubMed] [Google Scholar]
  • 39.Schmidt RE, Michon JM, Woronicz J. Enhancement of natural killer function through activation of the T11 E rosette receptor. J Clin Invest. 1987;79:305–305. doi: 10.1172/JCI112800. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Schmidt RE, Caulfield JP, Michon J. T11/CD2 activation of cloned human natural killer cells results in increased conjugate formation and exocytosis of cytolytic granules. J Immunol. 1988;140:991–991. [PubMed] [Google Scholar]
  • 41.Siziopikou KP, Harris JE, Casey L, Braun DP. Impaired tumoricidal function of alveolar macrophages from patients with nonsmall cell lung cancer. Cancer. 1991;68:1035–1035. doi: 10.1002/1097-0142(19910901)68:5<1035::AID-CNCR2820680522>3.0.CO;2-D. [DOI] [PubMed] [Google Scholar]
  • 42.Sone S. Role of alveolar macrophages in pulmonary neoplasias. Biochem Biophys Acta. 1986;823:227–227. doi: 10.1016/0304-419x(86)90004-1. [DOI] [PubMed] [Google Scholar]
  • 43.Stötter H, Wiebke EA, Tomita S, Belldegrun A, Topalian S, Rosenberg SA, Lotze MT. Cytokines alter target cell susceptibility to lysis. 2. Evaluation of tumor infiltrating lymphocytes. J Immunol. 1989;142:1767–1767. [PubMed] [Google Scholar]
  • 44.Sunshine G, Katz D, Czitron A. Heterogeneity of stimulator cells in the murine mixed leukocyte response. Eur J Immunol. 1982;12:9–9. doi: 10.1002/eji.1830120105. [DOI] [PubMed] [Google Scholar]
  • 45.Swinburne S, Moore M, Cole P. Human bronchoalveolar macrophage cytotoxicity for cultured human lung tumor cells. Br J Cancer. 1982;46:625–625. doi: 10.1038/bjc.1982.247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46.Thomassen MJ, Wiedemann HP, Barna BP, Farmer M, Ahmad M. Induction of in vitro tumoricidal activity in alveolar macrophages and monocytes from patients with lung cancer. Cancer Res. 1988;48:3949–3949. [PubMed] [Google Scholar]
  • 47.Tiefenthaler G, Hünig T, Dustin ML, Springer TA, Meuer SC. Purified lymphocyte function associated antigen-3 and T11 target structure are active in CD2 mediated T cell stimulation. Eur J Immunol. 1987;17:1847–1847. doi: 10.1002/eji.1830171227. [DOI] [PubMed] [Google Scholar]
  • 48.Wanebo HJ. Immunologic testing as a guide to cancer management. Surg Clin North Am. 1979;59:323–323. doi: 10.1016/s0039-6109(16)41788-3. [DOI] [PubMed] [Google Scholar]
  • 49.Weissler JC, Lipscomb MF, Lem VM, Toews GB. Tumor killing by human alveolar macrophages and blood monocytes: decreased cytotoxicity of human alveolar macrophages. Am Rev Repir Dis. 1986;134:532–532. doi: 10.1164/arrd.1986.134.3.532. [DOI] [PubMed] [Google Scholar]
  • 50.Weissler JC, Nicod LP, Toews GB. Pulmonary NK cell activity is reduced in patients with bronchogenic carcinoma. Am Rev Respir Dis. 1987;135:1353–1353. doi: 10.1164/arrd.1987.135.6.1353. [DOI] [PubMed] [Google Scholar]

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