Advertisement

Medical Oncology

, Volume 13, Issue 3, pp 133–140 | Cite as

Granulocyte-macrophage colony-stimulating factor and the immune system

  • Philip E. TarrEmail author
Article

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multifunctional cytokine currently used for the reversal of neutropenia associated with cytotoxic chemotherapy, bone marrow and haemopoietic stem cell transplantation. GM-CSF also modulates the function of differentiated white blood cells. In the context of local inflammatory responses, GM-CSF stimulates macrophages for antimicrobial and antitumor effects. GM-CSF further enhances healing and repair by its actions on hbroblasts and epidermal cells. GM-CSF is the pivotal mediator of the maturation and function of dendritic cells, the most important cell type for the induction of primary T cell immune responses. GM-CSF may enhance antibody dependent cellular cytotoxicity (ADCC) in several cell types, and the generation and cytotoxicity of natural killer (NK) cells. On this basis, GM-CSF may be useful for inducing or augmenting antibody responses to antimicrobial vaccines, to enhance killing of intracellular microorganisms, to accelerate epidermal and mucosal wound healing, and to stimulate protective immunity against tumors.

Keywords

GM-CSF cytokines immune system wound healing vaccine adjuvant cancer immunotherapy 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Marty, M. (ed.) (1996)Manual of GM-CSF. Oxford: Blackwell Science.Google Scholar
  2. 2.
    Jones, T.C. (1994) Future uses of granulocyte-macrophage colony-stimulating factor.Stem Cells 12, Suppl 1, 229–39.PubMedCrossRefGoogle Scholar
  3. 3.
    Ruef, C. and Coleman, D.L. (1990) GM-CSF: Pleiotropic cytokine with potential clinical usefulness.Rev. Inf. Dis. 12, 41–62.Google Scholar
  4. 4.
    Gasson, J.C. (1991) Molecular physiology of GM-CSF.Blood 11, 1131–45.Google Scholar
  5. 5.
    Bos, J.D. and Kapsenberg, ML. (1993) The skin immune system: progress in cutaneous biology.Immunol. Today 14, 75–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Matsue, H., Cruz, Jr, P.D., Bergstesser, P.R. and Takashima, A. (1992) Cytokine expression by epidermal cell subpopulations.J. Invest. Dermatol. 99, 42S-45S.PubMedCrossRefGoogle Scholar
  7. 7.
    Jung, H.C., Eckmann, L., Yang, S.K. et al. (1995) A distinct array of proinflammatory cytokines is expressed in human colon epithelial cells in response to bacterial invasion.J. Clin. Invest. 95, 55–65.PubMedCrossRefGoogle Scholar
  8. 8.
    Broide, D.H., Paine, MM. and Firestein, G.S. (1992) Eosinophils express interleukin-5 and granulocyte-macro- phage colony-stimulating factor mRNA at sites of allergic inflammation in asthmatics.J. Clin. Invest. 90, 1414–24.PubMedCrossRefGoogle Scholar
  9. 9.
    Kita, H., Ohnishi, T., Okubo, Y., Weiler, D. and Abrams, J.S. (1991) Granulocyte-macrophage colony-stimulating factor and interleukin-3 release from human peripheral blood eosinophils and neutrophils.J. Exp. Med. 174, 745–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Waellert, B., Desreumaux, P., Copin, M.C. et al.(1995) Immunoreactivity for interleukin 3 and 5 and granulocyte-macrophage colony-stimulating factor of intestinal mucosa in bronchial asthma.J. Exp. Med. 182, 1897–1904.CrossRefGoogle Scholar
  11. 11.
    Schreiber, R.D. and Chaplin, D.D. (1995) Cytokines, inflammation, and innate immunity. In M.M. Frank, K.F. Austen, H.N. Claman and E.R Unanue,Samter’s immunologic diseases, 5th edn, pp. 297–301. Boston: Little, Brown.Google Scholar
  12. 12.
    Dixon Gray J., Hirokawa, M. and Horwitz, D.A. (1994) The role of TGF/3 in the generation of suppression: An interaction between CD8+ T and NK cells.J. Exp. Med. 180, 1937–42.CrossRefGoogle Scholar
  13. 13.
    Hogasen, A.K., Hestdal, K., Hogasen, K. and Abrahamsen, T.G. (1995) Transforming growth factor beta modulates C3 and factor B synthesis and complement receptor 3 expression in cultured human monocytes.J. Leuk. Biol. 57, 287–96.Google Scholar
  14. 14.
    Cassatella, M.A., Meda, L., Bonora, S., Ceska, M. and Constantin, G. (1993) Interleukin-10 (IL-10) inhibits the release of proinflammatory cytokines from polymorphonuclear leukocytes. Evidence for an autocrine role of tumor necrosis factor and IL-1 beta in mediating the production of IL-8 triggered by lipopolysaccharide.J. Exp. Med. 178, 2207–11.PubMedCrossRefGoogle Scholar
  15. 15.
    Kurzrock, R., Talpaz, M. and Gutterman, J. (1992) Very low doses of GM-CSF administered alone or with erythropoietin in aplastic anemia.Am. J. Med. 93, 41–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Stewart-Akers, A.M., Cairns, J.S., Tweardy, DJ. and McCarthy, S.A. (1994) GM-CSF augmentation of T cell receptor dependent and T cell receptor independent thymocyte proliferation.Blood 83, 713–23.PubMedGoogle Scholar
  17. 17.
    Santoli, D., Clark, S.C., Kreider, B.L., Maslin, P.A. and Rovera, G. (1988) Amplification of IL-2 driven T cell proliferation by recombinant human IL-3 and GM-CSF.J. Immunol. 141, 519–26.PubMedGoogle Scholar
  18. 18.
    Burgess, A.W., Begley, C.G., Johnson, G.R. et al. (1987) Purification and properties of bacterially synthesized human GM-CSF.Blood 69, 443–51.Google Scholar
  19. 19.
    Tarr, P.E., Lin, R., Mueller, E. A., Kovarik, J.M., Guillaume, M. and Jones, T.C. (1996) Evaluation of tolerability and antibody response after recombinant human granulocyte- macrophage colony-stimulating factor (rhGM-CSF) and a single dose of recombinant hepatitis B vaccine.Vaccine,14, 1199–1204.PubMedCrossRefGoogle Scholar
  20. 20.
    Estey, E.H., Kurzrock, R., Talpaz, M. et al (1991) Effects of low doses of rhGM-CSF in patients with myelodysplastic syndromes.Br. J. Haematol. 77, 291–5.PubMedCrossRefGoogle Scholar
  21. 21.
    Jones, T., Stern, A. and Lin, R. (1994) Potential role of granulocyte-macrophage colony-stimulating factor as vaccine adjuvant.Eur. J. Clin. Microbiol. Infect. Dis. Suppl. 2, 47S-53S.CrossRefGoogle Scholar
  22. 22.
    Frenette, P.S. and Wagner, D.D. (1996) Adhesion molecules-part II: Blood vessels and blood cells.N. Engl. J. Med. 335, 43–5.PubMedCrossRefGoogle Scholar
  23. 23.
    Okahara, H., Yagita, H., Miyzke, K. and Okamura, K. (1994) Involvement of very late activation antigen 4 (VLA-4) and vascular adhesion molecule 1 (VCAM-1) in tumor necrosis factor a enhancement of experimental metastasis.Cancer Res. 54, 3233–6.PubMedGoogle Scholar
  24. 24.
    Coleman, D.L., Chodakewitz, J.A., Bartiss, A.H. and Mellors, J. W. (1988) GM-CSF enhances selective effector functions of tissue derived macrophages.Blood 72, 573–8.PubMedGoogle Scholar
  25. 25.
    Smith, P.D., Lamerson, C.L., Saini, S.S., Wahl, L.M., Calderone, R.A. and Wahl, S.M. (1990) Granulocytemacrophage colony-stimulating factor augments human monocyte fungicidal activity forCandida albicans.J. Infect. Dis. 161, 999–1005.PubMedGoogle Scholar
  26. 26.
    Bermudez, L.E., Martinelli, J., Petrovsky, M., Kolowski, P. and Young, L. (1994) Recombinant granulocyte-macrophage colony-stimulating factor enhances the effects of antibodies against mycobacterium avium complex infection in the beige mouse model.J. Infect. Dis. 169, 575–80.PubMedGoogle Scholar
  27. 27.
    Reed, S.G., Nathan, C.F., Pihl, D.L. et al. (1987) Recombinant granulocyte-macrophage colony-stimulating factor activates macrophages to inhibitTrypanosoma cruzi and release hydrogen peroxide: Comparison with interferon.J. Exp. Med. 166, 1734–46.PubMedCrossRefGoogle Scholar
  28. 28.
    Bodey, G.P., Anaissie, E., Gutterman, J. and Vadhan-Raj, S. (1993) Role of granulocyte-macrophage colony-stimulating factor as adjuvant therapy for fungal infection in patients with cancer.Clin. Inf. Dis. 17, 705–7.Google Scholar
  29. 29.
    Badaro, R., Nascimento, C, Carvalho, J. S. et al. (1994) Recombinant human granulocyte-macrophage colony-stimulating factor reverses neutropenia and reduces secondary infections in visceral leishmaniasis.J. Inf. Dis. 170, 413–8.Google Scholar
  30. 30.
    Senneville, E., Beuscart, C, Morand, P. et al. (1995) Sulfa- diazine-Pyrimethamine (SP) and granulocyte-macrophage colony-stimulating factor vs SP alone as treatment for central nervous toxoplasmosis in AIDS patients (abstract 1225). Prog. Abstr. 35th Intersci. Conf. on antimicrobial agents and chemotherapy, p. 245.San Francisco.Google Scholar
  31. 31.
    Charak, B.S., Agah, R. and Mazumder, A. (1993) GM-CSF induced ADCC in bone marrow macrophages: Application in bone marrow transplantation.Blood 81, 3474–9.PubMedGoogle Scholar
  32. 32.
    Kushner, B.H. and Cheung, N.K.V. (1989) GM-CSF enhances 3F8 monoclonal ADCC against human melanoma and neuroblastoma.Blood 73, 1936–41.PubMedGoogle Scholar
  33. 33.
    Masucci, G., Wersaell, P., Ragnhammar, P. and Mellstedt, H. (1989) GM-CSF augments the cytotoxic capacity of lymphocytes and monocytes in ADCC.Cancer Immunol. Immunother. 29, 288–92.PubMedCrossRefGoogle Scholar
  34. 34.
    Connor, R.I., Shen, L. and Fanger, M.W. (1990) Evaluation of the ADCC capabilities of individual human monocytes.J. Immunol 145, 1483–9.PubMedGoogle Scholar
  35. 35.
    Mellstedt, H., Fagerberg, J., Frö’din, J.E., Liljefors, M. and Ragnhammar, P. (1996) Colorectal cancer in section: clinical use in oncology. In M. Marty (ed.),Manual of GM-CSF, pp. 86–95. Oxford: Blackwell Science.Google Scholar
  36. 36.
    Grabstein, K.H., Urdal, D.L., Tushinski, R.J. et al. (1986) Induction of macrophage tumoricidal activity by granulocyte-macrophage colony-stimulating factor.Science 232, 506–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Kleinerman, E.S., Knowles, R.D., Lachman, L.B. and Gutterman, J. (1988) Effect of recombinant GM-CSF on human monocyte activityin vitro and following intravenous administration.Cancer Res. 48, 2604–9.PubMedGoogle Scholar
  38. 38.
    Grabstein, K.H. and Alderson, M.R. (1993) Regulation of macrophage tumoricidal activity by granulocyte-macrophage colony-stimulating factor. In R. Van Furth (ed.),Hemopoietic growth factors and mononuclear phagocytes, pp. 140–7. Basel: Karger.Google Scholar
  39. 39.
    Ho, A.D., Haas, R., Wulf, G. et al. (1990) Activation of lymphocytes induced by rhGM-CSF in patients with malignant lymphoma.Blood 75, 203–12.PubMedGoogle Scholar
  40. 40.
    Bendall, L.J., Kortlepel, K. and Gottlieb, DJ. (1995) GM- CSF enhances IL-2-activated natural killer cell lysis of clonogenic AML cells by upregulating target cell expression of ICAM-1.Leukemia 9, 677–84.PubMedGoogle Scholar
  41. 41.
    Scott, P. and Trinchieri, G. (1995) The role of natural killer cells in host-parasite interactions.Curr. Op. Immunol. 7, 34–40.CrossRefGoogle Scholar
  42. 42.
    Miller, J.S., Oelkers, S., Verfaillie, C. and McGlave, P. (1992) Role of monocytes in the expansion of human activated NK cells.Blood 80, 2221–9.PubMedGoogle Scholar
  43. 43.
    Schuurman, B., Beelen, R.HJ. and Meyer, S. (1996) Adjuvant treatment in surgery: colorectal cancer, in section: future uses. In M. Marty (ed.),Manual of GM-CSF. Oxford: Blackwell Science.Google Scholar
  44. 44.
    Levin, D., Constant, S., Pasqualini, T., Fla veil R. and Bottomly, K. (1993) Role of dendritic cells in the priming of CD4 + T lymphocytes to peptide antigenin vivo.J. Immunol. 151, 6742–50.PubMedGoogle Scholar
  45. 45.
    Young, J.W. and Steinman, R.M. (1990) Dendritic cells stimulate primary human cytolytic lymphocyte responses in the absence of CD4+ helper cells.J. Exp. Med. 171, 1315–22.PubMedCrossRefGoogle Scholar
  46. 46.
    Caux, C, Liu, Y.J. and Banchereau, J. (1995) Recent advances in the study of dendritic cells and follicular dendritic cells.Immunol. Today 16, 2–4.PubMedCrossRefGoogle Scholar
  47. 47.
    Croft, M. (1994) Activation of naive, memory, and effector T cells.Curr. Op. Immunol 6, 431–7.CrossRefGoogle Scholar
  48. 48.
    Berg, S.F.,. Mjaaland, S. and Fossum, S. (1994) Comparing macrophages and dendritic leukocytes as antigen presenting cells from humoral responsesin vivo and by antigen targeting.Eur. J. Immunol. 23, 1262–8.CrossRefGoogle Scholar
  49. 49.
    Kaplan, G., Walsh, G., Guido, L. S. et al (1992) Novel responses of human skin to intradermal recombinant granulocyte-macrophage colony-stimulating factor: Langerhans cell recruitment, keratinocyte growth, and enhanced wound healing.J. Exp. Med. 175, 1717–28.PubMedCrossRefGoogle Scholar
  50. 50.
    Sallusto, F. and Lanzavecchia, A. (1994) Efficient presentation of soluble antigen by cultured human Des is maintained by GM-CSF plus IL-4 and downregulated by TNF- α.J. Exp. Med. 179, 1109–18.PubMedCrossRefGoogle Scholar
  51. 51.
    Caux, C, Dezutter-Dambuyant, C, Schmitt, D. and Banchereau, J. (1992) GM-CSF and TNF-α cooperate in the generation of Langerhans cells.Nature 360, 258–61.PubMedCrossRefGoogle Scholar
  52. 52.
    Inaba, K., Inaba, M.; Romani, N. et al. (1992) Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with GM-CSF.J. Exp. Med. 176, 1693–1702.PubMedCrossRefGoogle Scholar
  53. 53.
    Marcowicz, S. and Engleman, E. (1990) Granulocyte-macrophage colony-stimulating factor promotes differentiation and survival of human peripheral blood dendritic cellsin vitro.J. Clin. Invest. 85, 955–61.CrossRefGoogle Scholar
  54. 54.
    Austyn, J. M. (1996) New Insights into the mobilization and phagocytic activity of dendritic cells.J. Exp. Med. 183, 1287–92.PubMedCrossRefGoogle Scholar
  55. 55.
    Fischer, H.G., Frosch, S., Reske, K. and Reske-Kunz, A.B. (1988) Granulocyte-macrophage colony-stimulating factor activates macrophages derived from bone marrow culture to synthesis of MHC class II molecules and to augmented antigen presentation function.J. Immunol 141, 3882–8.PubMedGoogle Scholar
  56. 56.
    Morrissey, P.J., Bressler, L., Park, L.S., Alpert, A. and Gillis, S. (1987) Granulocyte-macrophage colony-stimulating factor augments the primary antibody response by enhancing the function of antigen presenting cells.J. Immunol 139, 1113–9.PubMedGoogle Scholar
  57. 57.
    Alvaro-Garcia, j.M., Zvaifler, N.J. and Firestein, G.S. (1989) Cytokines in chronic inflammatory arthritis. IV. Granulocyte-macrophage colony-stimulating factor-mediated induction of class II MHC antigen on human monocytes: A possible role in rheumatoid arthritis.J. Exp. Med. 170, 865–75.CrossRefGoogle Scholar
  58. 58.
    Larsen, C.P., Ritchie, S.C., Hendrix, R. et al. (1994) Regulation of immunostimulatory function and costimulatory molecule (B7-1 and B7-2) expression in murine dendritic cells.J. Immunol. 152, 5208–19.PubMedGoogle Scholar
  59. 59.
    Mayordomo, J.I., Zorina, T., Storkus, W J. et al. (1995) Bone marrow derived dendritic cells pulsed with synthetic tumour peptides elicit protective and therapeutic antitumour immunity.Nature Med. 1, 1297–1302.PubMedCrossRefGoogle Scholar
  60. 60.
    Szabolcs, P., Moore, M.A.S. and Young, J.W. (1995) Expansion of immunostimulatory dendritic cells among myeloid progeny of human cd34+ bone marrow precursors, cultured with c-kit ligand, granulocyte-macrophage colony-stimulating factor, and TNF-a.J. Immunol 154, 5851–61.PubMedGoogle Scholar
  61. 61.
    Porcelli, S.A. and Modlin, R.L. (1995) CD1 and the expanding universe of T cell antigens.J. Immunol 155, 3709–10.PubMedGoogle Scholar
  62. 62.
    Kuendig, T.M., Bachmann, M.F., DiPaolo, C. et al (1995) Fibroblasts as efficient antigen presenting cells in lymphoid organs.Science 268, 1343–7.CrossRefGoogle Scholar
  63. 63.
    Zinkernagel, R. M. (1996) Immunology taught by viruses.Science 271, 173–8.PubMedCrossRefGoogle Scholar
  64. 64.
    Tarr, P.E., Lin, R. and Jones, T. C. (1996) Vaccine Adjuvancy, in section: Future uses. In M. Marty (ed.),Manual of GM-CSF, pp. 219–232. Oxford: Blackwell Science.Google Scholar
  65. 65.
    Liehl, E., Hildebrandt, J., Lam, C. and Mayer, P. (1994) Prediction of the role of granulocyte-macrophage colony- stimulating factor in animals and man from in vivo results.Eur. J. Clin. Microbiol Infect. Dis. 13, Suppl 2, 9S-17S.CrossRefGoogle Scholar
  66. 66.
    Tao, M.H. and Levy, R. (1993) Idiotype/granulocyte-macro- phage colony-stimulating factor fusion protein as a vaccine for B-cell lymphoma.Nature 362, 755–8.PubMedCrossRefGoogle Scholar
  67. 67.
    Loibner, H., Janzek, E., Mayer, P. and Liehl, E. (1995) Vaccination of rhesus monkeys with an anti-idiotype antibody mimicking Lewis Y: enhancement of the anti-tumor response by repeated administration of recombinant human GM-CSF. In Abstr. 10th Int. Conf. on monoclonal antibody immunoconjugates for cancer (abstr. 20). InAntibody Immunoconjugates Radiopharmaceut. 8, 64.Google Scholar
  68. 68.
    Hansen, P.B., Johnson, H.E. and Kippe, E. (1993) Autoimmune hypothyroidism and granulocyte-macrophage colony-stimulating factor.Eur. J. Haematol. 50, 183–4.PubMedGoogle Scholar
  69. 69.
    Nathan, F. E. and Besa, E. C. (1992) GM-CSF and accelerated hemolysis.N. Engl J. Med. 326, 417.PubMedGoogle Scholar
  70. 70.
    Dranoff, G., Jaffee, E., Lazenby, A. et al (1993) Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long lasting anti-tumor immunity.Proc. Natl Acad. Sci. USA 90, 3539–43.PubMedCrossRefGoogle Scholar
  71. 71.
    Sanda, M.G., Ayyagari, S.R., Jaffee, E.M. et al (1994) Demonstration of a rational strategy for human prostate cancer gene therapy.J. Urol 151, 622–8.PubMedGoogle Scholar
  72. 72.
    Berns, A.J.M., Clift, S., Cohen, L. K. et al (1995) Phase I study of non-replicating autologous tumor cell injections using cells prepared with or without GM-CSF gene transduction in patients with metastatic renal cell carcinoma.Hum. Gene Ther. 6, 347–68.PubMedCrossRefGoogle Scholar
  73. 73.
    Levitsky, H.I., Montgomery, J., Ahmadzadeh, M. et al (1996) Immunization with granulocyte-macrophage colony-stimulating factor-transduce, but not B7-1 transduced, lymphoma cells primes idiotype-specific T cells and generates potent systemic antitumor immunity.J. Immunol 156, 3858–65.PubMedGoogle Scholar
  74. 74.
    Meeker, T., Lowder, J., Clearly, M. L. et al (1985) Emergence of idiotype variants during treatment of B-cell lymphoma with anti-idiotype antibodies.N. Engl J. Med. 312, 1658–65.PubMedCrossRefGoogle Scholar
  75. 75.
    Garrido, F., Cabrera, T., Concha, A., Glew, S., Ruiz-Cabello, F. and Stern, P. L. (1993) Natural history of HLA expression during tumor development.Immunol. Today 14, 491–9.PubMedCrossRefGoogle Scholar
  76. 76.
    Wu, T.C., Huang, A.Y.C., Jaffee, E.M., Levitsky, H.I. and Pardoll, D.M. (1995) A reassessment of the role of B7-1 expression in tumor rejection.J. Exp. Med. 182, 1415–21.PubMedCrossRefGoogle Scholar
  77. 77.
    Bevan, MJ. (1995) Antigen presentation to cytotoxic T lymphocytesin vivo.J. Exp. Med. 182, 639–41.PubMedCrossRefGoogle Scholar
  78. 78.
    Suto, R. and Srivastava, P.K. (1995) A mechanism for the specific immunogenicity of heat shock protein-chaperoned peptides.Science 269, 1585–8.PubMedCrossRefGoogle Scholar
  79. 79.
    Falo, L.D., Kovacsovics-Bankowski, M., Thompson, K. and Rock, K. L. (1995) Targeting antigen into the phagocytic pathwayin vivo induces protective tumour immunity.Nature Med. 1, 649–53.PubMedCrossRefGoogle Scholar
  80. 80.
    Tan, K.C., Hosoi, J., Grabbe, S., Asahina, A. and Granstein, R. D. (1994) Epidermal cell presentation of tumor- associated antigens for induction of tolerance.J. Immunol. 153, 760–7.PubMedGoogle Scholar
  81. 81.
    Grabbe, S., Beissert, S., Schwarz, T. and Granstein, R. D. (1995) Dendritic cells as initiators of tumor immune responses: a possible strategy for tumor immunotherapy?Immunol. Today 16, 117–21.PubMedCrossRefGoogle Scholar
  82. 82.
    Hsu, F.J., Benike, C., Fagnoni, F. et al. (1996) Vaccination of patients with B-cell lymphoma using autologous antigen- pulsed dendritic cells.Nature Med. 2, 52–7.PubMedCrossRefGoogle Scholar
  83. 83.
    Zitvogel, L., Mayordomo, J.I., Tjandrawan, T. et al. (1996) Therapy of murine tumors with tumor peptide pulsed dendritic cells: Dependence on T cells, B7 costimulation and T helper cell 1-associated cytokines.J. Exp. Med. 183, 87–97.PubMedCrossRefGoogle Scholar
  84. 84.
    Celluzzi, CM., Mayordomo, J.I., Storkus, W.J., Lotze, M. T. and Falo, L. D. (1996) Peptide-pulsed dendritic cells induce antigen-specihc, CTL-mediated protective tumor immunity.J. Exp. Med. 183, 283–7.PubMedCrossRefGoogle Scholar
  85. 85.
    Paglia, P., Chiodoni, C., Rodolfo, M. and Colombo, M. P. (1996) Murine dendritic cells loadedin vitro with soluble protein prime cytotoxic T lymphocytes against tumor antigenin vivo.J. Exp. Med. 183, 317–322.PubMedCrossRefGoogle Scholar
  86. 86.
    Young, J. W. and Inaba, K. (1996) Dendritic cells as adjuvants for class I major histocompatibility complex-restricted antitumor immunity.J. Exp. Med. 183, 7–11.PubMedCrossRefGoogle Scholar
  87. 87.
    Mosmann, T. R. and Coffman, R.L. (1989) Thl and Th2 cells: Different patterns of lymphokine secretion lead to different functional properties.Ann. Rev. Immunol. 7, 145–73.CrossRefGoogle Scholar
  88. 88.
    Paul, W.E. and Seder, R.A. (1994) Lymphocyte responses and cytokines.Cell 76, 241–51.PubMedCrossRefGoogle Scholar
  89. 89.
    Katz, J.D., Benoist, C. and Mathis, D. (1995) T helper subsets in insulin dependent diabetes.Science 268, 1185–8.PubMedCrossRefGoogle Scholar
  90. 90.
    Hsieh, C.S., Macatortia, S.E., Tripp, C.S., Wolf, S.F.,O’Garra, A. and Murphy, K.M. (1993) Development of Thl CD4+ T cells through IL-12 produced by Listeria induced macrophages.Science 260, 547–9.PubMedCrossRefGoogle Scholar
  91. 91.
    Kuchroo, V.K., Das, M.P., Brown, J.A. et al. (1995) B7-1 and B7-2 costimulatory molecules activate differentially the Thl/Th2 development pathways: Application to autoimmune disease therapy.Cell 80, 707–18.PubMedCrossRefGoogle Scholar
  92. 92.
    Freeman, G.J., Boussiotis, V.A., Anumanthan, A. et al. (1995) B7-1 and B7-2 do not deliver identical costimulatory signals, since B7-2 but not B7-1 preferentially costimulates the initial production of IL-4.Immunity 2, 523–32.PubMedCrossRefGoogle Scholar
  93. 93.
    Maurer, D. and Stingl, G. (1996) Wound healing, in: section future uses. In M. Marty (ed.),Manual of GM-CSF, pp. 208–18, Oxford: Blackwell Scientific.Google Scholar
  94. 94.
    Lin, R., Tarr, P.E. and Jones, T.C. (1995) Present status of the use of cytokines as adjuvants to protect with vaccines against infectious diseases.Clin. Inf. Dis. 21, 1439–49.Google Scholar
  95. 95.
    Lin, R., Tarr, P.E. and Jones, T.C. (1996) Considerations regarding the use of cytokines in active specific immunotherapy of cancer.Vac. Res. 5, 41–51.Google Scholar
  96. 96.
    Lenardo, M.J. (1991) Interleukin-2 programs mouse alpha beta T lymphocytes for apoptosis.Nature 353, 858–61.PubMedCrossRefGoogle Scholar
  97. 97.
    Huang, Y.P., Pechere, J.C, Michel, M. et al. (1992)In vivo T cell activation,in vitro defective IL-2 secretion, and response to influenza vaccination in elderly women.J. Immunol. 148, 715–22.PubMedGoogle Scholar
  98. 98.
    Afonso, L.C.C., Scharton, T.M., Vieira, L.Q., Wysocka, M., Trinchieri, G. and Scott, P. (1994) The adjuvant effect of interleukin-12 in a vaccine againstLeishmania major.Science 263, 235–7.PubMedCrossRefGoogle Scholar
  99. 99.
    Adachi, T., Motojima, S., Hirata, A., Fukuda, T. and Makino, S. (1995) Eosinophil viability enhancing activity in sputum from patients with bronchial asthma: Contributions of interleukin-5 and granulocyte-macrophage colony- stimulating factor.Am. J. Respir. Crit. Care Med. 151, 618–23.PubMedGoogle Scholar
  100. 100.
    Frandji, P., Tcaczyk, C, Oskeritzian, C. et al. (1995) Presentation of soluble antigens by mast cells: Upregulation by interleukin-4 and granulocyte-macrophage colony-stimulating factor and downregulation by interferon-γ.Cell Immunol. 163, 37–46.PubMedCrossRefGoogle Scholar
  101. 101.
    Bratton, D.L., Hamid, Q., Boguniewicz, M., Doherty, D.E., Kaliey, J.M. and Leung, D.Y.M. (1995) Granulocyte-macrophage colony-stimulating factor contributes to enhanced monocyte survival in chronic atopic dermatitis.J. Clin. Invest. 95, 211–8.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 1996

Authors and Affiliations

  1. 1.Department of MedicineBeth Israel Deaconess Medical Center, West Campus, Harvard Medical SchoolBostonUSA

Personalised recommendations