Effect of prolactin on carcinoembryonic antigen-specific cytotoxic T lymphocyte response induced by dendritic cells
L. MATERA,
E. BELTRAMO,
E. MARTINUZZI,
S. BUTTIGLIERI,
L. MATERA
Department of Internal Medicine, University of Turin, and
Search for more papers by this authorE. BELTRAMO
Department of Internal Medicine, University of Turin, and
Search for more papers by this authorE. MARTINUZZI
Department of Internal Medicine, University of Turin, and
Search for more papers by this authorS. BUTTIGLIERI
Department of Oncology, Centro OncoEmatologicoSubalpino, Italy
Search for more papers by this authorL. MATERA,
E. BELTRAMO,
E. MARTINUZZI,
S. BUTTIGLIERI,
L. MATERA
Department of Internal Medicine, University of Turin, and
Search for more papers by this authorE. BELTRAMO
Department of Internal Medicine, University of Turin, and
Search for more papers by this authorE. MARTINUZZI
Department of Internal Medicine, University of Turin, and
Search for more papers by this authorS. BUTTIGLIERI
Department of Oncology, Centro OncoEmatologicoSubalpino, Italy
Search for more papers by this authorLina Matera, Laboratory of Tumor Immunology, Department of Internal Medicine, University of Turin, Corso AM Dogliotti, 14, 10126 Turin, Italy.
E-mail: [email protected]
SUMMARY
The cytokine hormone prolactin (PRL) has been shown previously to modulate native cellular responses and maturation of antigen-presenting cells. Here we have addressed its effect on the antigen-specific response of cytotoxic T lymphocytes (CTL). CTL were generated from HLA-A2 lymphocytes after three rounds of stimulation with autologous dendritic cells loaded with HLA-A2-restricted carcinoembrionic antigen (CEA) Cap-1 (YLSGANLNL) peptide. Selected cultures were expanded on cytokine-supplemented feeder-layers, enriched for CD8+ lymphocytes and analysed for PRL-receptor (PRL-R) expression and PRL responsiveness. Resting CD8+ lymphocytes were negative for PRL-R, whereas antigen-activated CD8+ lymphocytes derived from long-term cultures were highly positive. Results of a 51Cr release assay showed CTL killing of CEA-loaded, but not unloaded, T2 cell line and the CEA-positive gastric carcinoma cell line KATO, but not of the CEA-negative T leukaemia cell line Jurkat. Interferon (IFN)-γ release, evaluated in an ELISPOT assay against CEA-loaded T2, was enhanced (P < 0·05) by concentrations of PRL (12–25 ng/ml) very close to the physiological levels (6–20 ng/ml), but was decreased (P < 0·05) by high concentrations (200 ng/ml). Pre-incubation of the stimulators with the anti-MHC class I MoAb W6·32 induced a 40–60% decrease of the PRL-boosted IFN-γ release, thus proving the MHC restriction of the lymphocyte response. Cytotoxicity against CEA-loaded T2 and KATO cell lines was also increased by 12–25 ng (P < 0·05) and decreased (P < 0·05) by 200 ng PRL. Pre-incubation of CTL with an antibody specific for the PRL-R almost completely abrogated this effect.
REFERENCES
- 1 Kooijman R, Hooghe-Peters EL, Hooghe R. Prolactin, growth hormone, and insulin-like growth factor-I in the immune system. Adv Immunol 1996; 63: 377–454.
- 2 Matera L. Action of pituitary and lymphocyte prolactin. Neuroimmunomodulation 1997; 4: 171–80.
- 3
Yu-Lee LY.
Signal transduction by prolactin receptors. In: R Matera,
L Rapaport, eds.
Growth and lactogenic hormones. Neuroimmune biology, Vol. 2. Amsterdam: Elsevier, 2002: 111–22.
10.1016/S1567-7443(02)80011-4 Google Scholar
- 4 Russell DH, Kibler R, Matrisian L, Larson DF, Poulos B, Magun BE. Prolactin receptors on human T and B lymphocytes: antagonism of prolactin binding by cyclosporine. J Immunol 1985; 134: 3027–31.
- 5 Gagnerault MC, Touraine P, Savino W, Kelly PA, Dardenne M. Expression of prolactin receptors in murine lymphoid cells in normal and autoimmune situations. J Immunol 1993; 150: 5673–81.
- 6 Pellegrini I, Lebrun JJ, Ali S, Kelly PA. Expression of prolactin and its receptor in human lymphoid cells. Mol Endocrinol 1992; 6: 1023–31.
- 7 Whiteside TL, Herberman RB. The role of natural killer cells in immune surveillance of cancer. Curr Opin Immunol 1995; 7: 704–10.
- 8 Trinchieri G. Natural killer cells wear different hats: effector cells of innate resistance and regulatory cells of adaptive immunity and of hematopoiesis. Semin Immunol 1995; 7: 83–8.
- 9 Matera L, Muccioli G, Cesano A, Bellussi G, Genazzani E. Prolactin receptors on large granular lymphocytes: dual regulation by cyclosporin A. Brain Behav Immun 1988; 2: 1–10.
- 10 Matera LG, Bellone J, Lebrun PA et al. Role of prolactin in the in vitro development of interleukin-2-driven anti-tumoral lymphokine-activated killer cells. Immunology 1996; 89: 619–26.
- 11 Cesano A, Oberholtzer E, Contarini M, Geuna M, Bellone G, Matera L. Independent and synergistic effect of interleukin-2 and prolactin on development of T- and NK-derived LAK effectors. Immunopharmacology 1994; 28: 67–75.
- 12 Gaidano G, Contarini M, Pastore C, Saglio G, Matera L. AIDS-related Burkitt’s-type lymphomas are a target for lymphokine-activated killers induced by interleukin-2 and prolactin. P Soc Exp Biol Med 1996; 213: 196–205.
- 13
Matera L,
Buttiglieri S,
Moro F,
Geuna M.
Effect of prolactin on Natural Killer and MHC-restricted cytotoxic cells. In: R Matera,
L Rapaport, eds.
Growth and lactogenic hormones. Neuroimmune biology, Vol. 2. Amsterdam: Elsevier, 2002: 205–18.
10.1016/S1567-7443(02)80018-7 Google Scholar
- 14 Matera L, Galetto A, Geuna M et al. Individual and combined effect of GM-CSF and prolactin on maturation of dendritic cells from blood monocytes under serum-free conditions. Immunology 2000; 100: 29–36.
- 15 Matera L, Mori M, Geuna M, Buttiglieri S, Palestro G. Prolactin in autoimmunity and antitumor defence. J Neuroimmunol 2000; 109: 47–55.
- 16 Banchereau J, Steinman R. Dendritic cells and the control of immunity. Nature 1998; 392: 245–52.
- 17 Ridge JP, Di Rosa F, Matzinger P. A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell. Nature 1998; 393: 474–8.
- 18 Matera L, Cutufia M, Geuna M et al. Prolactin is an autocrine growth factor for the Jurkat human T leukemic cell line. J Neuroimmunol 1997; 79: 12–21.
- 19 Kooijman R, Gerlo S, Coppens A, Hooghe-Peters EL. Myeloid leukemic cells express and secrete bioactive pituitary-sized 23 kDa prolactin. J Neuroimmunol 2000; 110: 252–8.
- 20
Matera L,
Geuna M,
Pastore C et al.
Expression of prolactin and prolactin receptors by non-Hodgkin's lymphoma cells.
Int J Cancer
2000; 85: 124–30.
10.1002/(SICI)1097-0215(20000101)85:1<124::AID-IJC22>3.0.CO;2-U CAS PubMed Web of Science® Google Scholar
- 21 Ben-Jonathan N, Liby K, Mcfarland M, Zinger M. Prolactin as an autocrine/paracrine growth factor in human cancer. Trends Endocrinol Metab 2002; 13: 245–50.
- 22 Salazar-Onfray F. Interleukin-10: a cytokine used by tumors to escape immunosurveillance. Med Oncol 1999; 16: 86–94.
- 23 Freeman GJ, Sharpe AH, Kuchroo VK. Protect the killer: CTLs need defenses against the tumor. Nat Med 2002; 8: 787–9.
- 24 Salter RD, Howell DN, Cresswell P. Genes regulating HLA class I antigen expression in T B lymphoblast hybrids. Immunogenetics 1985; 21: 235–46.
- 25 Sekiguchi M, Sakakibara K, Fuji G. Establishment of cultured cell lines derived from a human gastric carcinoma. Jpn J Exp Med 1978; 48: 61–8.
- 26 Romani N, Reider D, Heuer M, Ener S, Eibl B, Schuler G. Generation of mature dendritic cells from human blood: an improved method with special regard to clinical applicability. J Immunol Meth 1996; 196: 137–51.
- 27 Buttiglieri S, Galetto A, Forno S, De Andrea M, Matera L. Influence of drug-induced apoptotic death on processing and presentation of tumor antigens by dendritic cells. Int J Cancer 2003; 106: 516–20.
- 28 Muraro R, Wunderlich D, Thor A et al. Definition by monoclonal antibodies of a repertoire of epitopes on carcinoembyonic antigen differentially expressed in human colon carcinomas versus normal human adult tissues. Cancer Res 1985; 45: 5769–80.
- 29 Walter EA, Greenberg PD, Gilbert MJ, Watanabe KS, Thomas ED, Riddell SR. Reconstitution of cellular immunity against cytomegalovirus in recipients of allogenic bone marrow by transfer of T-cell clones from the donor. N Engl J Med 1995; 333: 1038–44.
- 30
Nukaya I,
Yasumoto M,
Iwasaki T et al.
Identification of HLA-A24 epitope peptides of carcinoembryonic antigen which induce tumor-reactive cytotoxic T lymphocyte.
Int J Cancer
1999; 80: 92–7.
10.1002/(SICI)1097-0215(19990105)80:1<92::AID-IJC18>3.0.CO;2-M CAS PubMed Web of Science® Google Scholar
- 31 Pross HF, Baines MG, Rubin P, Shragge P, Petterson MS. Spontaneous human lymphocyte-mediated cytotoxicity against tumor target cells. IX. The quantitation of natural killer cells activity. J Clin Immunol 1981; 1: 51–64.
- 32 Herr W, Linn B, Leister N, Wandel E, Meyer zum Buschenfelde KH, Wolfel T. The use of computer-assisted video image analysis for the quantification of CD8+ T lymphocytes producing tumor necrosis factor alpha spots in response to peptide antigens. J Immunol Meth 1997; 203: 141–52.
- 33 Tsang KY, Zaremba S, Nieroda CA, Zhu MZ, Hamilton JM, Schlom J. Generation of human cytotoxic T cells specific for human carcinoembryonic antigen epitopes from patients immunized with recombinant vaccinia-CEA vaccine. J Natl Cancer Inst 1995; 87: 982–90.
- 34 Morse MA, Deng Y, Coleman D et al. A phase I study of active immunotherapy with carcinoembryonic antigen peptide (CAP-1)-pulsed, autologous human cultured dendritic cells in patients with metastatic malignancies expressing carcinoembryonic antigen. Clin Cancer Res 1999; 5: 1331–8.
- 35 Matera L, Contarini M, Bellone G, Forno B, Biglino A. Up-modulation of interferon-gamma mediates the enhancement of spontanous cytotoxicity in prolactin-activated natural killer cells. Immunology 1999; 98: 386–92.
- 36 Garner R, Helgason CD, Atkinson EA et al. Characterizazion of a granule-independent lytic mechanism used by CTL hybridomas. J Immunol 1994; 153: 5413–21.
- 37 Kagi D, Vignaux F, Ledermann B et al. Fas and perforin pathways as major mechanism of T cell-mediated cytotoxicity. Science 1994; 265: 528–30.
- 38 Yu-Lee L. Stimulation of interferon regulatory factor-1 by prolactin. Lupus 2001; 10: 691–9.
- 39 Dogusan Z, Book ML, Verdood P, Yu-Lee LY, Hooghe-Peters EL. Prolactin activates interferon regulatory factor-1 expression in normal lympho-hemopoietic cells. Eur Cytokine Netw 2000; 11: 435–42.
- 40 Duncan GS, Mattrucker HV, Kagi D, Matsuyama T, Mak TW. The transcription factor interferon regulatory factor-1 is essential for natural killer cell function in vivo. J Exp Med 1996; 184: 2043–8.
- 41 Krumenacker JS, Montgomery DW, Buckley DJ, Gout PW, Buckley AR. Prolactin receptor signaling: shared components with the T-cell antigen receptor in Nb2 lymphoma cells. Endocrine 1998; 9: 313–20.
- 42 Wells JA, De Vos AM. Structure and function of human growth hormon: implication for the hematopoietin. Ann Rev Biophys Biomol Struct 1993; 22: 329–51.
- 43
Hooghe R,
Devos S,
Dogusan Z,
Hooghe-Peters EL.
Signal transduction and modulation of gene expression by prolactin in human leukocytes. In: In: R Matera,
L Rapaport, eds.
Growth and lactogenic hormones. Neuroimmune biology, Vol. 2. Amsterdam: Elsevier, 2002: 123–36.
10.1016/S1567-7443(02)80012-6 Google Scholar
- 44 Goffin VN, Binart P, Clement-Lacroix B et al. From the molecular biology of prolactin and its receptor to the lessons learned from knockout mice models. Genet Anal 1999; 15: 189–201.
- 45 Bouchard B, Ormandy CJ, Di Santo JP, Kelly PA. Immune system development and function in prolactin receptor-deficient mice. J Immunol 1999; 163: 576–82.
- 46
Dorshkind K,
Horseman ND.
Anterior pituitary hormones, stress, and immune system homeostasis.
Bioessays
2001; 23: 288–94.
10.1002/1521-1878(200103)23:3<288::AID-BIES1039>3.0.CO;2-P CAS PubMed Web of Science® Google Scholar
- 47 Matera L, Mori M. Cooperation of pituitary hormone prolactin with interleukin-2 and interleukin-12 on production of interferon-gamma by natural killer and T cells. Ann NY Acad Sci 2000; 917: 503–13.
