| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Nonobese diabetic (NOD) mice spontaneously develop diabetes as a
consequence of an autoimmune process that can be inhibited by
immunotherapy with the 60-kDa heat shock protein (hsp60), with
its mycobacterial counterpart 65-kDa (hsp65), or with other Ags such as
insulin and glutamic acid decarboxylase (GAD). Microbial infection and
innate signaling via LPS or CpG motifs can also inhibit the spontaneous
diabetogenic process. In addition to the spontaneous disease, however,
NOD mice can develop a more robust cyclophosphamide-accelerated
diabetes (CAD). In this work, we studied the effect on CAD of DNA
vaccination with constructs encoding the Ags human hsp60 (phsp60) or
mycobacterial hsp65 (phsp65). Vaccination with phsp60 protected NOD
mice from CAD. In contrast, vaccination with phsp65, with an empty
vector, or with a CpG-positive oligonucleotide was not effective,
suggesting that the efficacy of the phsp60 construct might be based on
regulatory hsp60 epitopes not shared with its mycobacterial
counterpart, hsp65. Vaccination with phsp60 modulated the T cell
responses to hsp60 and also to the GAD and insulin autoantigens; T cell
proliferative responses were significantly reduced, and the pattern of
cytokine secretion to hsp60, GAD, and insulin showed an increase in
IL-10 and IL-5 secretion and a decrease in IFN-
secretion,
compatible with a shift from a Th1-like toward a Th2-like autoimmune
response. Our results extend the role of specific hsp60
immunomodulation in the control of 
cell autoimmunity and
demonstrate that immunoregulatory networks activated by specific phsp60
vaccination can spread to other Ags targeted during the progression of
diabetes, like insulin and GAD.
This article has been cited by other articles:
|
|
 |
|
  M. Cohen-Sfady, M. Pevsner-Fischer, R. Margalit, and I. R. Cohen Heat Shock Protein 60, via MyD88 Innate Signaling, Protects B Cells from Apoptosis, Spontaneous and Induced J. Immunol., July 15, 2009; 183(2): 890 - 896. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. J. Quintana, M. F. Farez, V. Viglietta, A. H. Iglesias, Y. Merbl, G. Izquierdo, M. Lucas, A. S. Basso, S. J. Khoury, C. F. Lucchinetti, et al. Antigen microarrays identify unique serum autoantibody signatures in clinical and pathologic subtypes of multiple sclerosis PNAS, December 2, 2008; 105(48): 18889 - 18894. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Jin, A. Zhu, Y. Wang, Q. Chen, Q. Xiong, J. Li, Y. Sun, T. Li, R. Cao, J. Wu, et al. A Th1-Recognized Peptide P277, When Tandemly Repeated, Enhances a Th2 Immune Response toward Effective Vaccines against Autoimmune Diabetes in Nonobese Diabetic Mice J. Immunol., January 1, 2008; 180(1): 58 - 63. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Cohen-Sfady, G. Nussbaum, M. Pevsner-Fischer, F. Mor, P. Carmi, A. Zanin-Zhorov, O. Lider, and I. R. Cohen Heat Shock Protein 60 Activates B Cells via the TLR4-MyD88 Pathway J. Immunol., September 15, 2005; 175(6): 3594 - 3602. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J. Quintana and I. R. Cohen Heat Shock Proteins as Endogenous Adjuvants in Sterile and Septic Inflammation J. Immunol., September 1, 2005; 175(5): 2777 - 2782. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zanin-Zhorov, G. Tal, S. Shivtiel, M. Cohen, T. Lapidot, G. Nussbaum, R. Margalit, I. R. Cohen, and O. Lider Heat Shock Protein 60 Activates Cytokine-Associated Negative Regulator Suppressor of Cytokine Signaling 3 in T Cells: Effects on Signaling, Chemotaxis, and Inflammation J. Immunol., July 1, 2005; 175(1): 276 - 285. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zanin-Zhorov, R. Bruck, G. Tal, S. Oren, H. Aeed, R. Hershkoviz, I. R. Cohen, and O. Lider Heat Shock Protein 60 Inhibits Th1-Mediated Hepatitis Model via Innate Regulation of Th1/Th2 Transcription Factors and Cytokines J. Immunol., March 15, 2005; 174(6): 3227 - 3236. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Ju, J. Liu, W. Xiao, M. Liu, and X. Qu Construction of a eukaryotic expression system of HSP65 gene from Mycobacterium tuberculosis, and anti-HSP65 IgG produced in mice J. Med. Microbiol., January 1, 2005; 54(1): 3 - 6. [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]
|
|
|
|
|
|
F. J. Quintana, P. H. Hagedorn, G. Elizur, Y. Merbl, E. Domany, and I. R. Cohen Functional immunomics: Microarray analysis of IgG autoantibody repertoires predicts the future response of mice to induced diabetes PNAS, October 5, 2004; 101(suppl_2): 14615 - 14621. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Lillicrap, R. C. Duggleby, J. C. Goodall, and J. S. H. Gaston T cell recognition of a highly conserved epitope in heat shock protein 60: self-tolerance maintained by TCR distinguishing between asparagine and aspartic acid Int. Immunol., March 1, 2004; 16(3): 405 - 414. [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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
