| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
and IL-121
*
University of Texas Health Science Center, San Antonio, TX 78284; and
Laboratory of Host Defenses, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892
An imbalance in the Th1- and Th2-type cytokine responses may allow
certain microbes to modify the host response to favor their own
persistence. We now show that infection/pulsing of human
CD34+ peripheral blood hemopoietic progenitor
cell-derived dendritic cells (DCs) with Leishmania donovani
promastigotes, Histoplasma capsulatum, and
Mycobacterium kansasii impairs the constitutive production
of IL-12 from these cells. Thus, strategies aimed at modulating a
dysregulated Th1/Th2 response to infection would be of great interest.
To both augment the host immune response and deliver potent
immunomodulatory cytokines such as IL-12 and IFN-
, our goal is to
develop a therapeutic strategy using genetically modified, microbial
Ag-pulsed DCs. Toward developing such immunotherapies, we used
retrovirus-mediated somatic gene transfer techniques to engineer human
DCs to secrete biologically active IL-12 and IFN-. DCs pulsed with
microbial antigens (e.g., leishmania and histoplasma Ags) were capable
of inducing proliferative responses in autologous CD4+
lymphocytes. CD4+ lymphocytes cocultured with
IL-12-transduced autologous DCs had enhanced Ag-specific proliferative
responses compared with CD4+ lymphocytes cocultured with
nontransduced or IFN-- transduced DCs. In this cell culture model
system we demonstrate that IL-12 has a negative effect on IL-4
secretion that is independent of its ability to induce IFN-
secretion. Taken together, these results indicate that IL-12-transduced
DCs may be specifically suited in inducing or down-modulating
Ag-specific Th1 or Th2 responses, respectively, and thus may be useful
as adjunctive therapy in those intracellular infections in which a
dominant Th1 response is critical for the resolution of infection.
This article has been cited by other articles:
|
|
 |
|
  S. Tavakoli, W. Schwerin, A. Rohwer, S. Hoffmann, S. Weyer, R. Weth, H. Meisel, H. Diepolder, M. Geissler, P. R. Galle, et al. Phenotype and function of monocyte derived dendritic cells in chronic hepatitis B virus infection J. Gen. Virol., October 1, 2004; 85(10): 2829 - 2836. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Ahuja, S. Zhao, T. Bellido, L. I. Plotkin, F. Jimenez, and L. F. Bonewald CD40 Ligand Blocks Apoptosis Induced by Tumor Necrosis Factor {alpha}, Glucocorticoids, and Etoposide in Osteoblasts and the Osteocyte-Like Cell Line Murine Long Bone Osteocyte-Y4 Endocrinology, May 1, 2003; 144(5): 1761 - 1769. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Berberich, J. R. Ramirez-Pineda, C. Hambrecht, G. Alber, Y. A. W. Skeiky, and H. Moll Dendritic Cell (DC)-Based Protection Against an Intracellular Pathogen Is Dependent Upon DC-Derived IL-12 and Can Be Induced by Molecularly Defined Antigens J. Immunol., March 15, 2003; 170(6): 3171 - 3179. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Palendira, A. T. Kamath, C. G. Feng, E. Martin, P. J. Chaplin, J. A. Triccas, and W. J. Britton Coexpression of Interleukin-12 Chains by a Self-Splicing Vector Increases the Protective Cellular Immune Response of DNA and Mycobacterium bovis BCG Vaccines against Mycobacterium tuberculosis Infect. Immun., April 1, 2002; 70(4): 1949 - 1956. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Newman and A. Holly Candida albicans Is Phagocytosed, Killed, and Processed for Antigen Presentation by Human Dendritic Cells Infect. Immun., November 1, 2001; 69(11): 6813 - 6822. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Handman Leishmaniasis: Current Status of Vaccine Development Clin. Microbiol. Rev., April 1, 2001; 14(2): 229 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Demangel, U. Palendira, C. G. Feng, A. W. Heath, A. G. D. Bean, and W. J. Britton Stimulation of Dendritic Cells via CD40 Enhances Immune Responses to Mycobacterium tuberculosis Infection Infect. Immun., April 1, 2001; 69(4): 2456 - 2461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Bodnar, N. V. Serbina, and J. L. Flynn Fate of Mycobacterium tuberculosis within Murine Dendritic Cells Infect. Immun., February 1, 2001; 69(2): 800 - 809. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Tang, M. D. Inman, N. van Rooijen, P. Yang, H. Shen, K. Matsumoto, and P. M. O'Byrne Th Type 1-Stimulating Activity of Lung Macrophages Inhibits Th2-Mediated Allergic Airway Inflammation by an IFN-{{gamma}}-Dependent Mechanism J. Immunol., February 1, 2001; 166(3): 1471 - 1481. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Gildea, R. E. Morris, and S. L. Newman Histoplasma capsulatum Yeasts Are Phagocytosed Via Very Late Antigen-5, Killed, and Processed for Antigen Presentation by Human Dendritic Cells J. Immunol., January 15, 2001; 166(2): 1049 - 1056. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Mosca, A. C. Hobeika, T. M. Clay, S. K. Nair, E. K. Thomas, M. A. Morse, and H. K. Lyerly A subset of human monocyte-derived dendritic cells expresses high levels of interleukin-12 in response to combined CD40 ligand and interferon-gamma treatment Blood, November 15, 2000; 96(10): 3499 - 3504. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Quinones, S. K. Ahuja, P. C. Melby, L. Pate, R. L. Reddick, and S. S. Ahuja Preformed Membrane-associated Stores of Interleukin (IL)-12 Are a Previously Unrecognized Source of Bioactive IL-12 That Is Mobilized within Minutes of Contact with an Intracellular Parasite J. Exp. Med., August 14, 2000; 192(4): 507 - 516. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-P. Min, R. Gorczynski, X.-Y. Huang, M. Kushida, P. Kim, M. Obataki, J. Lei, R. M. Suri, and M. S. Cattral Dendritic Cells Genetically Engineered to Express Fas Ligand Induce Donor-Specific Hyporesponsiveness and Prolong Allograft Survival J. Immunol., January 1, 2000; 164(1): 161 - 167. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Ahuja, R. L. Reddick, N. Sato, E. Montalbo, V. Kostecki, W. Zhao, M. J. Dolan, P. C. Melby, and S. K. Ahuja Dendritic Cell (DC)-Based Anti-Infective Strategies: DCs Engineered to Secrete IL-12 Are a Potent Vaccine in a Murine Model of an Intracellular Infection J. Immunol., October 1, 1999; 163(7): 3890 - 3897. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Jiang, D. M. Magee, and R. A. Cox Construction of a Single-Chain Interleukin-12-Expressing Retroviral Vector and Its Application in Cytokine Gene Therapy against Experimental Coccidioidomycosis Infect. Immun., June 1, 1999; 67(6): 2996 - 3001. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Mummidi, G. Catano, L. Lam, A. Hoefle, V. Telles, K. Begum, F. Jimenez, S. S. Ahuja, and S. K. Ahuja Extensive Repertoire of Membrane-bound and Soluble Dendritic Cell-specific ICAM-3-grabbing Nonintegrin 1 (DC-SIGN1) and DC-SIGN2 Isoforms. INTER-INDIVIDUAL VARIATION IN EXPRESSION OF DC-SIGN TRANSCRIPTS J. Biol. Chem., August 24, 2001; 276(35): 33196 - 33212. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
