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


     
 

This Article
Right arrow Full Text
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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Park, A. Y.
Right arrow Articles by Scott, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Park, A. Y.
Right arrow Articles by Scott, P.
The Journal of Immunology, 2000, 165: 896-902.
Copyright © 2000 by The American Association of Immunologists

IL-12 Is Required to Maintain a Th1 Response During Leishmania major Infection1

Audrey Y. Park, Brian D. Hondowicz2 and Phillip Scott3

Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104

IL-12 initiates Th1 cell development and cell-mediated immunity, but whether IL-12 contributes to the maintenance of a Th1 response is unclear. To address this question, we infected IL-12 p40-/- C57BL/6 mice with Leishmania major, an intracellular protozoan parasite controlled by a cell-mediated immune response, and simultaneously administered IL-12. Whereas untreated p40-/- mice developed an uncontrolled infection, p40-/- mice treated with IL-12 for the first 2 or 4 wk of infection developed a Th1 response and resolved their lesions. However, the induction of this protective Th1 cell response by IL-12 treatment was not associated with long term immunity. We observed that on rechallenge in the absence of IL-12, the mice exhibited a susceptible phenotype. In addition, without rechallenge, lesions in the IL-12-treated p40-/- mice developed several weeks after cessation of IL-12 treatment. In both cases, disease was associated with the loss of a Th1 response and the development of a Th2 response. Our observations are not limited to the C57BL/6 strain, because IL-12 treatment was also unable to provide lasting protection to p40-/- BALB/c mice. Finally, we found that although Th1 cells from healed wild-type C57BL/6 mice adoptively transferred protection to L. major-infected RAG-/- mice, they were unable to protect p40-/- mice. In conclusion, these studies provide the first demonstration that IL-12 is required not only to initiate Th1 cell development but also throughout infection to maintain a Th1 cell response and resistance to L. major.




This article has been cited by other articles:


Home page
 J. Immunol.Home page
N. Pakpour, C. Zaph, and P. Scott
The Central Memory CD4+ T Cell Population Generated during Leishmania major Infection Requires IL-12 to Produce IFN-{gamma}
J. Immunol., June 15, 2008; 180(12): 8299 - 8305.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
J. D. Price, K. R. Simpfendorfer, R. R. Mantena, J. Holden, W. R. Heath, N. van Rooijen, R. A. Strugnell, and O. L. C. Wijburg
Gamma Interferon-Independent Effects of Interleukin-12 on Immunity to Salmonella enterica Serovar Typhimurium
Infect. Immun., December 1, 2007; 75(12): 5753 - 5762.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
N. Nakano, C. Nishiyama, S. Kanada, Y. Niwa, N. Shimokawa, H. Ushio, M. Nishiyama, K. Okumura, and H. Ogawa
Involvement of mast cells in IL-12/23 p40 production is essential for survival from polymicrobial infections
Blood, June 1, 2007; 109(11): 4846 - 4855.
[Abstract] [Full Text] [PDF]

Home page
 J. Exp. Med.Home page
H. Soares, H. Waechter, N. Glaichenhaus, E. Mougneau, H. Yagita, O. Mizenina, D. Dudziak, M. C. Nussenzweig, and R. M. Steinman
A subset of dendritic cells induces CD4+ T cells to produce IFN-{gamma} by an IL-12-independent but CD70-dependent mechanism in vivo
J. Exp. Med., May 14, 2007; 204(5): 1095 - 1106.
[Abstract] [Full Text] [PDF]

Home page
 J. Exp. Med.Home page
A. T. Shamshiev, F. Ampenberger, B. Ernst, L. Rohrer, B. J. Marsland, and M. Kopf
Dyslipidemia inhibits Toll-like receptor-induced activation of CD8{alpha}-negative dendritic cells and protective Th1 type immunity
J. Exp. Med., February 19, 2007; 204(2): 441 - 452.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
L. Buonaguro, M. L. Tornesello, M. Tagliamonte, R. C. Gallo, L. X. Wang, R. Kamin-Lewis, S. Abdelwahab, G. K. Lewis, and F. M. Buonaguro
Baculovirus-derived human immunodeficiency virus type 1 virus-like particles activate dendritic cells and induce ex vivo T-cell responses.
J. Virol., September 1, 2006; 80(18): 9134 - 9143.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. Nembrini, B. Abel, M. Kopf, and B. J. Marsland
Strong TCR Signaling, TLR Ligands, and Cytokine Redundancies Ensure Robust Development of Type 1 Effector T Cells.
J. Immunol., June 15, 2006; 176(12): 7180 - 7188.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Wuthrich, T. Warner, and B. S. Klein
IL-12 Is Required for Induction but Not Maintenance of Protective, Memory Responses to Blastomyces dermatitidis: Implications for Vaccine Development in Immune-Deficient Hosts
J. Immunol., October 15, 2005; 175(8): 5288 - 5297.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. G. Feng, D. Jankovic, M. Kullberg, A. Cheever, C. A. Scanga, S. Hieny, P. Caspar, G. S. Yap, and A. Sher
Maintenance of Pulmonary Th1 Effector Function in Chronic Tuberculosis Requires Persistent IL-12 Production
J. Immunol., April 1, 2005; 174(7): 4185 - 4192.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
Y. F. Vanloubbeeck, A. E. Ramer, F. Jie, and D. E. Jones
CD4+ Th1 Cells Induced by Dendritic Cell-Based Immunotherapy in Mice Chronically Infected with Leishmania amazonensis Do Not Promote Healing
Infect. Immun., August 1, 2004; 72(8): 4455 - 4463.
[Abstract] [Full Text] [PDF]

Home page
 J. Exp. Med.Home page
N. Wang, A. Satoskar, W. Faubion, D. Howie, S. Okamoto, S. Feske, C. Gullo, K. Clarke, M. R. Sosa, A. H. Sharpe, et al.
The Cell Surface Receptor SLAM Controls T Cell and Macrophage Functions
J. Exp. Med., May 3, 2004; 199(9): 1255 - 1264.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
D. Nolt and J. L. Flynn
Interleukin-12 Therapy Reduces the Number of Immune Cells and Pathology in Lungs of Mice Infected with Mycobacterium tuberculosis
Infect. Immun., May 1, 2004; 72(5): 2976 - 2988.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
A. R. Mathers and C. F. Cuff
Role of Interleukin-4 (IL-4) and IL-10 in Serum Immunoglobulin G Antibody Responses following Mucosal or Systemic Reovirus Infection
J. Virol., April 1, 2004; 78(7): 3352 - 3360.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. E. Uzonna, G. F. Spath, S. M. Beverley, and P. Scott
Vaccination with Phosphoglycan-Deficient Leishmania major Protects Highly Susceptible Mice from Virulent Challenge without Inducing a Strong Th1 Response
J. Immunol., March 15, 2004; 172(6): 3793 - 3797.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
N. Ismail, L. Soong, J. W. McBride, G. Valbuena, J. P. Olano, H.-M. Feng, and D. H. Walker
Overproduction of TNF-{alpha} by CD8+ Type 1 Cells and Down-Regulation of IFN-{gamma} Production by CD4+ Th1 Cells Contribute to Toxic Shock-Like Syndrome in an Animal Model of Fatal Monocytotropic Ehrlichiosis
J. Immunol., February 1, 2004; 172(3): 1786 - 1800.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S.-J. Ha, D.-J. Kim, K.-H. Baek, Y.-D. Yun, and Y.-C. Sung
IL-23 Induces Stronger Sustained CTL and Th1 Immune Responses Than IL-12 in Hepatitis C Virus Envelope Protein 2 DNA Immunization
J. Immunol., January 1, 2004; 172(1): 525 - 531.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
U. M. Padigel, N. Kim, Y. Choi, and J. P. Farrell
TRANCE-RANK Costimulation is Required for IL-12 Production and the Initiation of a Th1-Type Response to Leishmania major Infection in CD40L-Deficient Mice
J. Immunol., November 15, 2003; 171(10): 5437 - 5441.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
E. Muraille, C. De Trez, B. Pajak, F. A. Torrentera, P. De Baetselier, O. Leo, and Y. Carlier
Amastigote Load and Cell Surface Phenotype of Infected Cells from Lesions and Lymph Nodes of Susceptible and Resistant Mice Infected with Leishmania major
Infect. Immun., May 1, 2003; 71(5): 2704 - 2715.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
E. Muraille, C. De Trez, M. Brait, P. De Baetselier, O. Leo, and Y. Carlier
Genetically Resistant Mice Lacking MyD88-Adapter Protein Display a High Susceptibility to Leishmania major Infection Associated with a Polarized Th2 Response
J. Immunol., April 15, 2003; 170(8): 4237 - 4241.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
U. M. Padigel and J. P. Farrell
CD40-CD40 Ligand Costimulation Is Not Required for Initiation and Maintenance of a Th1-Type Response to Leishmania major Infection
Infect. Immun., March 1, 2003; 71(3): 1389 - 1395.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
D. Artis, K. Speirs, K. Joyce, M. Goldschmidt, J. Caamano, C. A. Hunter, and P. Scott
NF-{kappa}B1 Is Required for Optimal CD4+ Th1 Cell Development and Resistance to Leishmania major
J. Immunol., February 15, 2003; 170(4): 1995 - 2003.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. M. Cleary, W. Tu, A. Enright, T. Giffon, R. Dewaal-Malefyt, K. Gutierrez, and D. B. Lewis
Impaired Accumulation and Function of Memory CD4 T Cells in Human IL-12 Receptor {beta}1 Deficiency
J. Immunol., January 1, 2003; 170(1): 597 - 603.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
G. C. Pien, K. B. Nguyen, L. Malmgaard, A. R. Satoskar, and C. A. Biron
A Unique Mechanism for Innate Cytokine Promotion of T Cell Responses to Viral Infections
J. Immunol., November 15, 2002; 169(10): 5827 - 5837.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
Y.-J. Jung, R. LaCourse, L. Ryan, and R. J. North
Evidence Inconsistent with a Negative Influence of T Helper 2 Cells on Protection Afforded by a Dominant T Helper 1 Response against Mycobacterium tuberculosis Lung Infection in Mice
Infect. Immun., November 1, 2002; 70(11): 6436 - 6443.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
F. Aguilar Torrentera, J. D. Laman, M. Van Meurs, L. Adorini, E. Muraille, and Y. Carlier
Endogenous Interleukin-12 Is Critical for Controlling the Late but Not the Early Stage of Leishmania mexicana Infection in C57BL/6 Mice
Infect. Immun., September 1, 2002; 70(9): 5075 - 5080.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
B. John, D. Rajagopal, A. Pashine, S. Rath, A. George, and V. Bal
Role of IL-12-Independent and IL-12-Dependent Pathways in Regulating Generation of the IFN-{gamma} Component of T Cell Responses to Salmonella typhimurium
J. Immunol., September 1, 2002; 169(5): 2545 - 2552.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. Y. Park, B. Hondowicz, M. Kopf, and P. Scott
The Role of IL-12 in Maintaining Resistance to Leishmania major
J. Immunol., June 1, 2002; 168(11): 5771 - 5777.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
K. Dabbagh, M. E. Dahl, P. Stepick-Biek, and D. B. Lewis
Toll-Like Receptor 4 Is Required for Optimal Development of Th2 Immune Responses: Role of Dendritic Cells
J. Immunol., May 1, 2002; 168(9): 4524 - 4530.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. S. MacDonald and E. J. Pearce
Cutting Edge: Polarized Th Cell Response Induction by Transferred Antigen-Pulsed Dendritic Cells Is Dependent on IL-4 or IL-12 Production by Recipient Cells
J. Immunol., April 1, 2002; 168(7): 3127 - 3130.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. M. Cooper, A. Kipnis, J. Turner, J. Magram, J. Ferrante, and I. M. Orme
Mice Lacking Bioactive IL-12 Can Generate Protective, Antigen-Specific Cellular Responses to Mycobacterial Infection Only if the IL-12 p40 Subunit Is Present
J. Immunol., February 1, 2002; 168(3): 1322 - 1327.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. E. Uzonna, G. Wei, D. Yurkowski, and P. Bretscher
Immune Elimination of Leishmania major in Mice: Implications for Immune Memory, Vaccination, and Reactivation Disease
J. Immunol., December 15, 2001; 167(12): 6967 - 6974.
[Abstract] [Full Text] [PDF]

Home page
 J. Exp. Med.Home page
Y. Belkaid, K. F. Hoffmann, S. Mendez, S. Kamhawi, M. C. Udey, T. A. Wynn, and D. L. Sacks
The Role of Interleukin (IL)-10 in the Persistence of Leishmania major in the Skin after Healing and the Therapeutic Potential of Anti-IL-10 Receptor Antibody for Sterile Cure
J. Exp. Med., November 19, 2001; 194(10): 1497 - 1506.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
U. M. Padigel, P. J. Perrin, and J. P. Farrell
The Development of a Th1-Type Response and Resistance to Leishmania major Infection in the Absence of CD40-CD40L Costimulation
J. Immunol., November 15, 2001; 167(10): 5874 - 5879.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2000 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2000 by The American Association of Immunologists, Inc. All rights reserved.