Advertisement

Cancer Immunology, Immunotherapy

, Volume 33, Issue 1, pp 45–49 | Cite as

Interleukin-4 augments the cytotoxic capacity of lymphocytes and monocytes in antibody-dependent cellular cytotoxicity

  • Peter Wersäll
  • Giuseppe Masucci
  • Håkan Mellstedt
Original articles

Summary

Human peripheral blood mononuclear cells (lymphocytes and monocytes) (PBMC) were preincubated for 0–24 h with human recombinant interleukin-4 (IL-4) and used as effector cells in an 18 h antibody-dependent cellular cytotoxicity (ADCC) assay with mAb 17-1A (mouse IgG2A) against SW948 (a human colorectal carcinoma cell line). A statistically significant increase in the lytic capability was noted after 2–24 h of preactivation. IL-4 at 1 ng/ml induced the highest cell lysis while higher and lower concentrations were inferior or had no effect at all. Preactivation for 24 h induced a more effective lytic cell population than 2 h prestimulation: 63 LU (lytic units)/106 cells vs 42 LU/106 cells. Pretreatment with 1 ng/ml IL-4 for 2 h induced a statistically significant increase in the ADCC activity of PBMC (P <0.05), of monocytes (P <0.01) and E-rosette-negative cells (natural killer cells) (P <0.05) compared to non-activated cells. IL-4 did not induce lymphokine-activated killer activity of PBMC against SW948. The spontaneous cytotoxicity against K562 was, however, increased after stimulation with 1 ng/ml IL-4 for 2 h of E-rosette-negative non-adherent cells.

Key words

IL-4 ADCC Monoclonal antibodies 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Adams DO, Hall T, Steplewski Z, Koprowski H (1984) Tumors undergoing rejection induced by monoclonal antibodies of the IgG2a isotope contain increased numbers of macrophages activated for a distinctive form of antibody-dependent cytolysis. Proc Natl Acad Sci USA 81: 3506Google Scholar
  2. 2.
    Bøyum A (1983) Isolation of human blood monocytes with Nycodenz, a new non-ionic iodinated gradient medium. Scand J Immunol 17: 429Google Scholar
  3. 3.
    Coffman RL, Ohara J, Bond MW, Cartz J, Zlotnik A, Paul WE (1986) B-cell stimulatory factor-1 enhances the IgE response of lipopolysaccharide-activated B cells. J Immunol 136: 4538Google Scholar
  4. 4.
    Crawford RM, Finbloom DS, Ohara J, Paul WE, Meltzer MS (1987) B-cell stimulatory factor-1 (interleukin 4) activates macrophages for increased tumoricidal activity and expression of Ia antigens. J Immunol 139: 135Google Scholar
  5. 5.
    Fanger MW, Shen L, Graziano RF, Guyre PM (1989) Cytotoxicity mediated by human Fc receptors for IgG. Immunol Today 10: 92Google Scholar
  6. 6.
    Fernandez-Botran R, Sanders VM, Oliver K, Chen YW, Krammer PH, Uhr JW, Vitetta ES (1986) Interleukin 4 mediates autocrine growth of helper T cells after antigenic stimulation. Proc Natl Acad Sci USA 83: 9689Google Scholar
  7. 7.
    Frödin J-E, Pihlstedt P, Lefvert A-K, Mellstedt H (1987) Isolation and characterization of autologous blood mononuclear cells used for auto-infusion together with monoclonal antibodies in tumor treatment. Hybridoma 6: 555Google Scholar
  8. 8.
    Herlyn D, Herlyn M, Steplewski Z, Koprowski H (1979) Monoclonal antibodies in cell-mediated cytotoxicity against human melanoma and colorectal carcinoma. Eur J Immunol 9: 657Google Scholar
  9. 9.
    Janson CH, Tehrani MJ, Mellstedt H, Wigzell H (1989) Anti-idiotypic monoclonal antibody to a T-cell chronic lymphatic leukemia. Characterization of the antibody, in vitro effector functions and results of therapy. Cancer Immunol Immunother 28: 225Google Scholar
  10. 10.
    Julius MH, Simpson E, Herzenberg LA (1973) A rapid method for the isolation of functional thymus derived murine lymphocytes. Eur J Immunol 3: 645Google Scholar
  11. 11.
    Johnson W, Steplewski Z, Matthews TJ, Hamilton T, Koprowski H, Adams D (1986) Cytolytic interaction between murine macrophages, tumor cells and monoclonal antibodies: characterization of lytic condition and requirements for effector activation. J Immunol 136: 4704Google Scholar
  12. 12.
    Kawakami Y, Rosenberg SA, Lotze MT (1988) Interleukin 4 promotes the growth of tumor-infiltrating lymphocytes cytotoxic for human autologous melanoma. J Exp Med 168: 2183Google Scholar
  13. 13.
    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: 3452Google Scholar
  14. 14.
    Lindemalm C, Mellstedt H, Biberfeld P, Björkholm M, Christensson B, Holm G, Johansson B, Sundblad R (1983) Blood and lymph node T lymphocyte subsets in non-Hodgkin lymphomas. Scand J Haematol 30: 68Google Scholar
  15. 15.
    Ljunggren HD, Kärre K (1990) In search of the “missing self”: MHC molecules and NK cell recognition. Immunol Today 11: 237Google Scholar
  16. 16.
    Lundgren G, Zukoski CF, Möller G (1968) Differential effects of human granulocytes and lymphocytes on human fibroblasts. Clin Exp Immunol 3: 817Google Scholar
  17. 17.
    Masucci G, Masucci MG, Klein E (1982) Human blood lymphocyte subsets separated on the basis of nylon adherence, SRBC and EA rosetting: natural cytotoxicity and characterization with monoclonal reagents. Cell Immunol 69: 166Google Scholar
  18. 18.
    Masucci G, Lindemalm C, Frödin J-E, Hagström B, Mellstedt H (1988) Effect of human blood mononuclear cell populations in antibody dependent cellular cytotoxicity (ADCC) using two murine (CO17-1A and Br55-2) and one chimeric (17-1A) monoclonal antibodies against a human colorectal carcinoma cell line (SW948). Hybridoma 7: 429Google Scholar
  19. 19.
    Masucci G, Wersäll P, Ragnhammar P, Mellstedt H (1989) GM-CSF augments the cytotoxic capacity of lymphocytes and monocytes in antibody dependent cellular cytotoxicity (ADCC). Cancer Immunol Immunother 29: 288Google Scholar
  20. 20.
    Mitchell LC, Davis LS, Lipsky PE (1989) Promotion of human T lymphocyte proliferation by IL-4. J Immunol 142: 1548Google Scholar
  21. 21.
    Mosmann TR, Bond MW, Coffman RL, Ohara J, Paul WE (1986) T cell and mast cell lines respond to B cell stimulatory factor 1. Proc Natl Acad Sci USA 83: 5654Google Scholar
  22. 22.
    Vitetta ES, Brooks K, Chen YW, Isaksson P, Jones S, Layton J, Mishra GC, Pure E, Weiss E, Word C (1984) T cell derived lymphokines that induce IgM and IgG secretion in activated murine B cells. Immunol Rev 78: 137Google Scholar
  23. 23.
    Mule JJ, Krosnick JA, Rosenberg SA (1989) IL-4 regulation of murine lymphokine activated killer activity in vitro. Effects on the IL-2 induced expansion, cytotoxicity and phenotype of lymphokine activated killer effectors. J Immunol 142: 726Google Scholar
  24. 24.
    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: 2349Google Scholar
  25. 25.
    Noelle R, Krammer PH, Ohara J, Uhr JW, Vitetta ES (1984) Increased expression of Ia antigens on resting B cells: an additional role for B-cell growth factor. Proc Natl Acad Sci USA 81: 6149Google Scholar
  26. 26.
    Ortaldo J, Woodhouse C, Morgan AC, Herberman R, Cheresh D, Reisfeld R (1987) Analysis of effectors in human antibody-dependent cellular cytotoxicity with murine monoclonal antibodies. J Immunol 138: 3566Google Scholar
  27. 27.
    Peace DJ, Kern DE, Schultz KR, Greenberg PD, Cheever MA (1988) IL-4 induced lymphokine-activated killer cells. Lytic activity is mediated by phenotypically distinct natural killer-like and T cell-like large granular lymphocytes. J Immunol 140: 3679Google Scholar
  28. 28.
    Pfeifer JD, McKenzie DT, Swain S, Dutton RW (1987) B-cell stimulatory factor 1 (interleukin 4) is sufficient for the proliferation and differentiation of lectin-stimulated cytolytic T lymphocyte precursors. J Exp Med 166: 1464Google Scholar
  29. 29.
    Schulz G, Staffileno LK, Reisfeld RA, Dennert G (1985) Eradication of established human melanoma tumor in nude mice by antibody-directed effector cells. J Exp Med 161: 1315Google Scholar
  30. 30.
    Shetye J, Frödin J-E, Christensson B, Grant C, Jacobsson B, Sundelius S, Sylvén M, Biberfeld P, Mellstedt H (1988) Immunohistochemical monitoring of metastatic colorectal carcinoma in patients treated withmonoclonal antibodies (mAb 17-1A). Cancer Immunol Immunother 27: 154Google Scholar
  31. 31.
    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: 29Google Scholar
  32. 32.
    Velde AA, Klomp JPG, Yard BA, de Vries JE, Figdor CG (1988) Modulation of phenotypic and funcional properties of human peripheral blood monocytes by IL-4. J Immunol 140: 1548Google Scholar

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • Peter Wersäll
    • 1
  • Giuseppe Masucci
    • 1
  • Håkan Mellstedt
    • 1
  1. 1.Department of Oncology (Radiumhemmet) and Immunologic Research LaboratoryKarolinska HospitalStockholmSweden

Personalised recommendations