The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cesano, A.
Right arrow Articles by Santoli, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cesano, A.
Right arrow Articles by Santoli, D.

The Journal of Immunology, Vol 151, Issue 6 2943-2957, Copyright © 1993 by American Association of Immunologists

ARTICLES

Cellular and molecular mechanisms of activation of MHC nonrestricted cytotoxic cells by IL-12

A Cesano, S Visonneau, SC Clark and D Santoli
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.

Freshly separated PBL and two IL-2-dependent clonal T cell lines (TALL- 103/2 [TCR-gamma delta+] and TALL-104 [TCR-alpha beta+]) were used to dissect, at the cellular and molecular levels, the mechanisms governing the enhancing effects of IL-12 on MHC nonrestricted cytotoxic activity. IL-12 induced cytotoxicity both in PBL and TALL cells, although less efficiently than IL-2, and the two cytokines displayed additive effects. Unlike IL-2, IL-12 failed to enhance the CD3 or CD2 redirected killing of the TALL cell lines. Analysis of the percentage of E/T conjugates induced by these cytokines showed that IL-12 could increase PBL, but not TALL cell, binding only when used in combination with IL- 2. This and the failure of IL-12 to increase the expression of several adhesion molecules on PBL and TALL cells indicated no significant role for IL-12 in the binding step of the lytic interaction. We also excluded that production of TNF-alpha, IFN-gamma, or IL-2 by the IL-12- activated effectors might account for the cytotoxicity-inducing effects of this cytokine. By contrast, IL-12 was found to induce cytotoxic granule formation in PBL and TALL cells and to up-regulate the expression of their cytolytic components, including perforin, serine esterases, and TIA-1, both at the protein and mRNA levels. The costimulatory action of IL-2 and IL-12 on granulogenesis and induction of cytolytic proteins correlated well with the additive effects on cytotoxicity. Studies with cyclohexamide and actinomycin D demonstrated that TALL cells but not PBL require de novo protein synthesis for expression of serine esterases and perforin mRNA after IL-2 and/or IL- 12 stimulation, and that both cytokines act directly or indirectly at the transcriptional level. Overall, these data indicate that IL-12 acts mostly at a postbinding level of the lytic interaction, involving enhanced expression of cytotoxic mediators, and that IL-2 and IL-12 use partially distinct pathways to activate the MHC nonrestricted killer function of mature T cells and resting lymphocytes.


This article has been cited by other articles:


Home page
 Mol. Pharmacol.Home page
N. Methot, D. Guay, J. Rubin, D. Ethier, K. Ortega, S. Wong, D. Normandin, C. Beaulieu, T. J. Reddy, D. Riendeau, et al.
In Vivo Inhibition of Serine Protease Processing Requires a High Fractional Inhibition of Cathepsin C
Mol. Pharmacol., June 1, 2008; 73(6): 1857 - 1865.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
C. Brando, S. Mukhopadhyay, E. Kovacs, R. Medina, P. Patel, T. L. Catina, K. S. Campbell, and D. Santoli
Receptors and lytic mediators regulating anti-tumor activity by the leukemic killer T cell line TALL-104
J. Leukoc. Biol., August 1, 2005; 78(2): 359 - 371.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T. Satoh, T. Saika, S. Ebara, N. Kusaka, T. L. Timme, G. Yang, J. Wang, V. Mouraviev, G. Cao, E. M. A. Fattah, et al.
Macrophages Transduced with an Adenoviral Vector Expressing Interleukin 12 Suppress Tumor Growth and Metastasis in a Preclinical Metastatic Prostate Cancer Model
Cancer Res., November 15, 2003; 63(22): 7853 - 7860.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. De Creus, K. Van Beneden, F. Stevenaert, V. Debacker, J. Plum, and G. Leclercq
Developmental and Functional Defects of Thymic and Epidermal V{gamma}3 Cells in IL-15-Deficient and IFN Regulatory Factor-1-Deficient Mice
J. Immunol., June 15, 2002; 168(12): 6486 - 6493.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
A. P. Makrigiannis, B. L. Musgrave, S. M. M. Haeryfar, and D. W. Hoskin
Interleukin-12 can replace CD28-dependent T-cell costimulation during nonspecific cytotoxic T lymphocyte induction by anti-CD3 antibody
J. Leukoc. Biol., January 1, 2001; 69(1): 113 - 122.
[Abstract] [Full Text]

Home page
 Cancer Res.Home page
C. A. Kruse, S. Visonneau, B. K. Kleinschmidt-DeMasters, C. J. Gup, G. G. Gomez, D. B. Paul, and D. Santoli
The Human Leukemic T-Cell Line, TALL-104, Is Cytotoxic to Human Malignant Brain Tumors and Traffics through Brain Tissue: Implications for Local Adoptive Immunotherapy
Cancer Res., October 1, 2000; 60(20): 5731 - 5739.
[Abstract] [Full Text]

Home page
 Clin. Cancer Res.Home page
S. Visonneau, A. Cesano, D. L. Porter, S. L. Luger, L. Schuchter, M. Kamoun, M. H. Torosian, K. Duffy, C. Sickles, E. A. Stadtmauer, et al.
Phase I Trial of TALL-104 Cells in Patients with Refractory Metastatic Breast Cancer
Clin. Cancer Res., May 1, 2000; 6(5): 1744 - 1754.
[Abstract] [Full Text] [PDF]

Home page
 Neuro Oncol DukeHome page
B. Geoerger, C.-B. Tang, A. Cesano, S. Visonneau, S. Marwaha, K. D. Judy, L. N. Sutton, D. Santoli, and P. C. Phillips
Antitumor activity of a human cytotoxic T-cell line (TALL-104) in brain tumor xenografts
Neuro-oncol, April 1, 2000; 2(2): 103 - 113.
[Abstract] [PDF]

Home page
 JEMHome page
T. Kaisho, H. Tsutsui, T. Tanaka, T. Tsujimura, K. Takeda, T. Kawai, N. Yoshida, K. Nakanishi, and S. Akira
Impairment of Natural Killer Cytotoxic Activity and Interferon {gamma} Production in Ccaat/Enhancer Binding Protein {gamma}-Deficient Mice
J. Exp. Med., December 6, 1999; 190(11): 1573 - 1582.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. Visonneau, A. Cesano, K. A. Jeglum, and D. Santoli
Adjuvant Treatment of Canine Osteosarcoma with the Human Cytotoxic T-Cell Line TALL-104
Clin. Cancer Res., July 1, 1999; 5(7): 1868 - 1875.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Y. Hyodo, K. Matsui, N. Hayashi, H. Tsutsui, S.-i. Kashiwamura, H. Yamauchi, K. Hiroishi, K. Takeda, Y.-i. Tagawa, Y. Iwakura, et al.
IL-18 Up-Regulates Perforin-Mediated NK Activity Without Increasing Perforin Messenger RNA Expression by Binding to Constitutively Expressed IL-18 Receptor
J. Immunol., February 1, 1999; 162(3): 1662 - 1668.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
W. E. Fogler, K. Volker, M. Watanabe, J. M. Wigginton, P. Roessler, M. J. Brunda, J. R. Ortaldo, and R. H. Wiltrout
Recruitment of Hepatic NK Cells by IL-12 Is Dependent on IFN-{gamma} and VCAM-1 and Is Rapidly Down-Regulated by a Mechanism Involving T Cells and Expression of Fas
J. Immunol., December 1, 1998; 161(11): 6014 - 6021.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. De Jonge, C. Heirman, M. d. Veerman, S. Van Meirvenne, M. Moser, O. Leo, and K. Thielemans
In Vivo Retargeting of T Cell Effector Function by Recombinant Bispecific Single Chain Fv (Anti-CD3 Anti-Idiotype) Induces Long-Term Survival in the Murine BCL1 Lymphoma Model
J. Immunol., August 1, 1998; 161(3): 1454 - 1461.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
B. Bussolati, F. Mariano, A. Cignetti, A. Guarini, V. Cambi, R. Foa, G. Piccoli, and G. Camussi
Platelet-Activating Factor Synthesized by IL-12-Stimulated Polymorphonuclear Neutrophils and NK Cells Mediates Chemotaxis
J. Immunol., August 1, 1998; 161(3): 1493 - 1500.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. S. Tannenbaum, R. Tubbs, D. Armstrong, J. H. Finke, R. M. Bukowski, and T. A. Hamilton
The CXC Chemokines IP-10 and Mig Are Necessary for IL-12-Mediated Regression of the Mouse RENCA Tumor
J. Immunol., July 15, 1998; 161(2): 927 - 932.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
E. J. McFarland, P. A. Harding, S. MaWhinney, R. T. Schooley, and D. R. Kuritzkes
In Vitro Effects of IL-12 on HIV-1-Specific CTL Lines from HIV-1-Infected Children
J. Immunol., July 1, 1998; 161(1): 513 - 519.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. D. Gillies, Y. Lan, J. S. Wesolowski, X. Qian, R. A. Reisfeld, S. Holden, M. Super, and K.-M. Lo
Antibody-IL-12 Fusion Proteins Are Effective in SCID Mouse Models of Prostate and Colon Carcinoma Metastases
J. Immunol., June 15, 1998; 160(12): 6195 - 6203.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. Cesano, S. Visonneau, S. Deaglio, F. Malavasi, and D. Santoli
Role of CD38 and Its Ligand in the Regulation of MHC-Nonrestricted Cytotoxic T Cells
J. Immunol., February 1, 1998; 160(3): 1106 - 1115.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
A. B. Geldhof, M. Moser, L. Lespagnard, K. Thielemans, and P. De Baetselier
Interleukin-12-Activated Natural Killer Cells Recognize B7 Costimulatory Molecules on Tumor Cells and Autologous Dendritic Cells
Blood, January 1, 1998; 91(1): 196 - 206.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
M. J. Robertson and J. Ritz
Interleukin 12: Basic Biology and Potential Applications in Cancer Treatment
Oncologist, February 1, 1996; 1(1): 88 - 97.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 1993 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 1993 by The American Association of Immunologists, Inc. All rights reserved.