Natural killer cell stimulatory factor (interleukin 12 [IL-12]) induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4-producing Th cells

doi:10.1084/jem.177.4.1199

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Natural killer cell stimulatory factor (interleukin 12 [IL-12]) induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4-producing Th cells

R Manetti, P Parronchi, MG Giudizi, MP Piccinni, E Maggi, G Trinchieri and S Romagnani
Division of Clinical Immunology and Allergy, University of Florence, Italy.

The effects exerted on the in vitro development of antigen-specific T cell lines and T cell clones by addition or neutralization of interleukin 12 (IL-12) in lymphocyte bulk culture were examined. T cell lines specific for Dermatophagoides pteronyssinus group I (Der p I) derived in the presence of IL-12 exhibited reduced ability to produce IL-4 and increased ability to produce interferon gamma (IFN-gamma), and developed into Der p I-specific CD4+ T cell clones showing a T helper type 0 (Th0)- or Th1-, instead of Th2-, like cytokine profile. In contrast, purified protein derivative (PPD)-specific T cell lines derived in the presence of anti-IL-12 antibody exhibited an increased ability to produce IL-4 and developed into PPD-specific CD4+ T cell clones showing a Th0-, instead of Th1-, like profile. The influence of IL-12 on the cytokine secretion profile of Der p I-specific T cell lines was not prevented by addition to lymphocyte bulk cultures of anti- IFN-gamma antibody, but could be at least partially inhibited by the removal from bulk cultures of CD16+ cells. Thus, IL-12 and CD16+ cells appear to have inhibitory effects on the development of IL-4-producing cells and to play an inductive role in promoting Th1-like responses.
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Khan, W. I., Blennerhassett, P. A., Deng, Y., Gauldie, J., Vallance, B. A., Collins, S. M. (2001). IL-12 gene transfer alters gut physiology and host immunity in nematode-infected mice. Am. J. Physiol. Gastrointest. Liver Physiol. 281: G102-G110 [Abstract] [Full Text]
Maeyama, T., Kuwano, K., Kawasaki, M., Kunitake, R., Hagimoto, N., Hara, N. (2001). Attenuation of bleomycin-induced pneumopathy in mice by monoclonal antibody to interleukin-12. Am. J. Physiol. Lung Cell. Mol. Physiol. 280: L1128-L1137 [Abstract] [Full Text]
Pertl, U., Luster, A. D., Varki, N. M., Homann, D., Gaedicke, G., Reisfeld, R. A., Lode, H. N. (2001). IFN-{{gamma}}-Inducible Protein-10 Is Essential for the Generation of a Protective Tumor-Specific CD8 T Cell Response Induced by Single-Chain IL-12 Gene Therapy. J. Immunol. 166: 6944-6951 [Abstract] [Full Text]
Li, W., Lu, L., Wang, Z., Wang, L., Fung, J. J., Thomson, A. W., Qian, S. (2001). IL-12 Antagonism Enhances Apoptotic Death of T Cells Within Hepatic Allografts from Flt3 Ligand-Treated Donors and Promotes Graft Acceptance. J. Immunol. 166: 5619-5628 [Abstract] [Full Text]
Park, J.-W., Gruys, M. E., McCormick, K., Lee, J.-K., Subleski, J., Wigginton, J. M., Fenton, R. G., Wang, J.-M., Wiltrout, R. H. (2001). Primary Hepatocytes from Mice Treated with IL-2/IL-12 Produce T Cell Chemoattractant Activity that Is Dependent on Monokine Induced by IFN-{{gamma}} (Mig) and Chemokine Responsive to {{gamma}}-2 (Crg-2). J. Immunol. 166: 3763-3770 [Abstract] [Full Text]
Das, L., Datta, N., Bandyopadhyay, S., Das, P. K. (2001). Successful Therapy of Lethal Murine Visceral Leishmaniasis with Cystatin Involves Up-Regulation of Nitric Oxide and a Favorable T Cell Response. J. Immunol. 166: 4020-4028 [Abstract] [Full Text]
TIMOSHANKO, J. R., KITCHING, A. R., HOLDSWORTH, S. R., TIPPING, P. G. (2001). Interleukin-12 from Intrinsic Cells Is an Effector of Renal Injury in Crescentic Glomerulonephritis. J. Am. Soc. Nephrol. 12: 464-471 [Abstract] [Full Text]
Marchant, A., Amedei, A., Azzurri, A., Vekemans, J., Benagiano, M., Tamburini, C., Lienhardt, C., Corrah, T., McAdam, K. P. W. J., Romagnani, S., D'Elios, M. M., Del Prete, G. (2001). Polarization of PPD-Specific T-Cell Response of Patients with Tuberculosis from Th0 to Th1 Profile after Successful Antimycobacterial Therapy or In Vitro Conditioning with Interferon-{alpha} or Interleukin-12. Am. J. Respir. Cell Mol. Bio. 24: 187-194 [Abstract] [Full Text]
Wigginton, J. E., Kirschner, D. (2001). A Model to Predict Cell-Mediated Immune Regulatory Mechanisms During Human Infection with Mycobacterium tuberculosis. J. Immunol. 166: 1951-1967 [Abstract] [Full Text]
Ishimitsu, R., Nishimura, H., Yajima, T., Watase, T., Kawauchi, H., Yoshikai, Y. (2001). Overexpression of IL-15 In Vivo Enhances Tc1 Response, Which Inhibits Allergic Inflammation in a Murine Model of Asthma. J. Immunol. 166: 1991-2001 [Abstract] [Full Text]
Infante-Duarte, C., Horton, H. F., Byrne, M. C., Kamradt, T. (2000). Microbial Lipopeptides Induce the Production of IL-17 in Th Cells. J. Immunol. 165: 6107-6115 [Abstract] [Full Text]
Silver, P. B., Hathcock, K. S., Chan, C.-C., Wiggert, B., Caspi, R. R. (2000). Blockade of Costimulation Through B7/CD28 Inhibits Experimental Autoimmune Uveoretinitis, But Does Not Induce Long-Term Tolerance. J. Immunol. 165: 5041-5047 [Abstract] [Full Text]
Murphy, T. L., Geissal, E. D., Farrar, J. D., Murphy, K. M. (2000). Role of the Stat4 N Domain in Receptor Proximal Tyrosine Phosphorylation. Mol. Cell. Biol. 20: 7121-7131 [Abstract] [Full Text]
Chang, C.-C. J., Wright, A., Punnonen, J. (2000). Monocyte-Derived CD1a+ and CD1a- Dendritic Cell Subsets Differ in Their Cytokine Production Profiles, Susceptibilities to Transfection, and Capacities to Direct Th Cell Differentiation. J. Immunol. 165: 3584-3591 [Abstract] [Full Text]
Plummeridge, M J, Armstrong, L, Birchall, M A, Millar, A B (2000). Reduced production of interleukin 12 by interferon gamma primed alveolar macrophages from atopic asthmatic subjects. Thorax 55: 842-847 [Abstract] [Full Text]
Schmitt, D. A., Ullrich, S. E. (2000). Exposure to Ultraviolet Radiation Causes Dendritic Cells/Macrophages to Secrete Immune-Suppressive IL-12p40 Homodimers. J. Immunol. 165: 3162-3167 [Abstract] [Full Text]
Worth, L. L., Jia, S.-F., Zhou, Z., Chen, L., Kleinerman, E. S. (2000). Intranasal Therapy with an Adenoviral Vector Containing the Murine Interleukin-12 Gene Eradicates Osteosarcoma Lung Metastases. Clin. Cancer Res. 6: 3713-3718 [Abstract] [Full Text]
Cai, G., Radzanowski, T., Villegas, E. N., Kastelein, R., Hunter, C. A. (2000). Identification of STAT4-Dependent and Independent Mechanisms of Resistance to Toxoplasma gondii. J. Immunol. 165: 2619-2627 [Abstract] [Full Text]
Smyth, M. J., Taniguchi, M., Street, S. E. A. (2000). The Anti-Tumor Activity of IL-12: Mechanisms of Innate Immunity That Are Model and Dose Dependent. J. Immunol. 165: 2665-2670 [Abstract] [Full Text]
Varga, E. M., Wachholz, P., Nouri-Aria, K. T., Verhoef, A., Corrigan, C. J., Till, S. J., Durham, S. R. (2000). T Cells from Human Allergen-Induced Late Asthmatic Responses Express IL-12 Receptor {beta}2 Subunit mRNA and Respond to IL-12 In Vitro. J. Immunol. 165: 2877-2885 [Abstract] [Full Text]
Cong, Y., Weaver, C. T., Lazenby, A., Elson, C. O. (2000). Colitis Induced by Enteric Bacterial Antigen-Specific CD4+ T Cells Requires CD40-CD40 Ligand Interactions for a Sustained Increase in Mucosal IL-12. J. Immunol. 165: 2173-2182 [Abstract] [Full Text]