| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and
Howard Hughes Medical Institute-National Institutes of Health Research Scholars Program, Bethesda, MD 20814
The mechanism of action of microbial adjuvants in promoting the differentiation of autoimmune effector cells remains to be elucidated. We demonstrate that CpG-containing oligodeoxynucleotides (ODN) can completely substitute for heat-killed mycobacteria in the priming of encephalitogenic myelin-reactive T cells in vivo. The adjuvanticity of the CpG ODN was secondary to their direct ability to induce IL-12 or to act synergistically with endogenous IL-12 to promote Th1 differentiation and encephalitogenicity. T cells primed in the absence of CpG with Ag and IFA alone appeared to be in a transitional state and had not undergone differentiation along a conventional Th pathway. Unlike Th2 cells, they expressed low levels of the IL-12Rß2 subunit and retained the ability to differentiate into encephalitogenic effectors when reactivated in vitro under Th1-polarizing conditions. These results support the use of CpG ODN as adjuvants but also suggest that they could potentially trigger autoimmune disease in a susceptible individual.
This article has been cited by other articles:
|
|
 |
|
  J. T. Tigno-Aranjuez, R. Jaini, V. K. Tuohy, P. V. Lehmann, and M. Tary-Lehmann Encephalitogenicity of Complete Freund's Adjuvant Relative to CpG Is Linked to Induction of Th17 Cells J. Immunol., November 1, 2009; 183(9): 5654 - 5661. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Kroenke, T. J. Carlson, A. V. Andjelkovic, and B. M. Segal IL-12- and IL-23-modulated T cells induce distinct types of EAE based on histology, CNS chemokine profile, and response to cytokine inhibition J. Exp. Med., July 7, 2008; 205(7): 1535 - 1541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Lampropoulou, K. Hoehlig, T. Roch, P. Neves, E. C. Gomez, C. H. Sweenie, Y. Hao, A. A. Freitas, U. Steinhoff, S. M. Anderton, et al. TLR-Activated B Cells Suppress T Cell-Mediated Autoimmunity J. Immunol., April 1, 2008; 180(7): 4763 - 4773. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Asagiri, T. Hirai, T. Kunigami, S. Kamano, H.-J. Gober, K. Okamoto, K. Nishikawa, E. Latz, D. T. Golenbock, K. Aoki, et al. Cathepsin K-Dependent Toll-Like Receptor 9 Signaling Revealed in Experimental Arthritis Science, February 1, 2008; 319(5863): 624 - 627. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Herrmann, M. Kellert, A. Spreer, J. Gerber, H. Eiffert, M. Prinz, and R. Nau Minocycline delays but does not attenuate the course of experimental autoimmune encephalomyelitis in Streptococcus pneumoniae-infected mice J. Antimicrob. Chemother., January 1, 2007; 59(1): 74 - 79. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Touil, D. Fitzgerald, G.-X. Zhang, A. Rostami, and B. Gran Cutting Edge: TLR3 Stimulation Suppresses Experimental Autoimmune Encephalomyelitis by Inducing Endogenous IFN-beta J. Immunol., December 1, 2006; 177(11): 7505 - 7509. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Herrmann, M. Kellert, H. Schmidt, A. Mildner, U. K. Hanisch, W. Bruck, M. Prinz, and R. Nau Streptococcus pneumoniae Infection Aggravates Experimental Autoimmune Encephalomyelitis via Toll-Like Receptor 2. Infect. Immun., August 1, 2006; 74(8): 4841 - 4848. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. V. Bagaeva, P. Rao, J. M. Powers, and B. M. Segal CXC chemokine ligand 13 plays a role in experimental autoimmune encephalomyelitis. J. Immunol., June 15, 2006; 176(12): 7676 - 7685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Su, P. B. Silver, R. S. Grajewski, R. K. Agarwal, J. Tang, C.-C. Chan, and R. R. Caspi Essential Role of the MyD88 Pathway, but Nonessential Roles of TLRs 2, 4, and 9, in the Adjuvant Effect Promoting Th1-Mediated Autoimmunity J. Immunol., November 15, 2005; 175(10): 6303 - 6310. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Wang, S. A. John, J. L. Clements, D. H. Percy, K. P. Barton, and L. A. Garrett-Sinha Ets-1 deficiency leads to altered B cell differentiation, hyperresponsiveness to TLR9 and autoimmune disease Int. Immunol., September 1, 2005; 17(9): 1179 - 1191. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Li, J. S. Heuser, S. D. Kosanke, M. Hemric, and M. W. Cunningham Protection against Experimental Autoimmune Myocarditis Is Mediated by Interleukin-10-Producing T Cells that Are Controlled by Dendritic Cells Am. J. Pathol., July 1, 2005; 167(1): 5 - 15. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Visser, H. Jan de Heer, L. A. Boven, D. van Riel, M. van Meurs, M.-J. Melief, U. Zahringer, J. van Strijp, B. N. Lambrecht, E. E. Nieuwenhuis, et al. Proinflammatory Bacterial Peptidoglycan as a Cofactor for the Development of Central Nervous System Autoimmune Disease J. Immunol., January 15, 2005; 174(2): 808 - 816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Zipris, E. Lien, J. X. Xie, D. L. Greiner, J. P. Mordes, and A. A. Rossini TLR Activation Synergizes with Kilham Rat Virus Infection to Induce Diabetes in BBDR Rats J. Immunol., January 1, 2005; 174(1): 131 - 142. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Darabi, A. Y. Karulin, B. O. Boehm, H. H. Hofstetter, Z. Fabry, J. C. LaManna, J. C. Chavez, M. Tary-Lehmann, and P. V. Lehmann The Third Signal in T Cell-Mediated Autoimmune Disease? J. Immunol., July 1, 2004; 173(1): 92 - 99. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Conant and R. H. Swanborg Autoreactive T Cells Persist in Rats Protected against Experimental Autoimmune Encephalomyelitis and Can Be Activated through Stimulation of Innate Immunity J. Immunol., May 1, 2004; 172(9): 5322 - 5328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Shao, S. Lei, S. L. Sun, J. Xiang, H. J. Kaplan, and D. Sun CpG-Containing Oligodeoxynucleotide 1826 Converts the Weak Uveitogenic Rat Interphotoreceptor Retinoid-Binding Protein Peptide 1181-1191 into a Strong Uveitogen J. Immunol., November 1, 2003; 171(9): 4780 - 4785. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. P. Ho, P. Fontoura, P. J. Ruiz, L. Steinman, and H. Garren An Immunomodulatory GpG Oligonucleotide for the Treatment of Autoimmunity via the Innate and Adaptive Immune Systems J. Immunol., November 1, 2003; 171(9): 4920 - 4926. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Lundberg, P. Welander, X. Han, and E. Cantin Herpes Simplex Virus Type 1 DNA Is Immunostimulatory In Vitro and In Vivo J. Virol., October 15, 2003; 77(20): 11158 - 11169. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Gursel, M. Gursel, H. Yamada, K. J. Ishii, F. Takeshita, and D. M. Klinman Repetitive Elements in Mammalian Telomeres Suppress Bacterial DNA-Induced Immune Activation J. Immunol., August 1, 2003; 171(3): 1393 - 1400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Steinman Optic Neuritis, A New Variant of Experimental Encephalomyelitis, A Durable Model for All Seasons, Now In Its Seventieth Year J. Exp. Med., May 5, 2003; 197(9): 1065 - 1071. [Full Text] [PDF]
|
|
|
|
|
|
C. Deng, C. Radu, A. Diab, M. F. Tsen, R. Hussain, J. S. Cowdery, M. K. Racke, and J. A. Thomas IL-1 Receptor-Associated Kinase 1 Regulates Susceptibility to Organ-Specific Autoimmunity J. Immunol., March 15, 2003; 170(6): 2833 - 2842. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. T. Ichikawa, L. P. Williams, and B. M. Segal Activation of APCs Through CD40 or Toll-Like Receptor 9 Overcomes Tolerance and Precipitates Autoimmune Disease J. Immunol., September 1, 2002; 169(5): 2781 - 2787. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Dalpke, M. K.-H. Schafer, M. Frey, S. Zimmermann, J. Tebbe, E. Weihe, and K. Heeg Immunostimulatory CpG-DNA Activates Murine Microglia J. Immunol., May 15, 2002; 168(10): 4854 - 4863. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Lassmann, C. Kincaid, V. C. Asensio, and I. L. Campbell Induction of Type 1 Immune Pathology in the Brain Following Immunization Without Central Nervous System Autoantigen in Transgenic Mice With Astrocyte-Targeted Expression of IL-12 J. Immunol., November 1, 2001; 167(9): 5485 - 5493. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Howard and S. D. Miller Autoimmune Intervention by CD154 Blockade Prevents T Cell Retention and Effector Function in the Target Organ J. Immunol., February 1, 2001; 166(3): 1547 - 1553. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
