Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Focus on Europe

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 24 March 2006:
Vol. 311. no. 5768, pp. 1775 - 1778
DOI: 10.1126/science.1124004
Prev | Table of Contents | Next

Reports

Islet Recovery and Reversal of Murine Type 1 Diabetes in the Absence of Any Infused Spleen Cell Contribution

Junko Nishio, Jason L. Gaglia, Stuart E. Turvey,* Christopher Campbell, Christophe Benoist,{dagger} Diane Mathis{dagger}

A cure for type 1 diabetes will probably require the provision or elicitation of new pancreatic islet ß cells as well as the reestablishment of immunological tolerance. A 2003 study reported achievement of both advances in the NOD mouse model by coupling injection of Freund's complete adjuvant with infusion of allogeneic spleen cells. It was concluded that the adjuvant eliminated anti-islet autoimmunity and the donor splenocytes differentiated into insulin-producing (presumably ß) cells, culminating in islet regeneration. Here, we provide data indicating that the recovered islets were all of host origin, reflecting that the diabetic NOD mice actually retain substantial ß cell mass, which can be rejuvenated/regenerated to reverse disease upon adjuvant-dependent dampening of autoimmunity.

Section on Immunology and Immunogenetics, Joslin Diabetes Center, and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, and Harvard Stem Cell Institute, 1 Joslin Place, Boston, MA 02215, USA.

* Present address: Division of Infectious and Immunological Diseases, Children's Hospital, Vancouver, British Columbia V6H 3V4, Canada.

{dagger} To whom correspondence should be addressed. E-mail: cbdm{at}joslin.harvard.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Innocuous IFN{gamma} induced by adjuvant-free antigen restores normoglycemia in NOD mice through inhibition of IL-17 production.
R. Jain, D. M. Tartar, R. K. Gregg, R. D. Divekar, J. J. Bell, H.-H. Lee, P. Yu, J. S. Ellis, C. M. Hoeman, C. L. Franklin, et al. (2008)
J. Exp. Med. 205, 207-218
   Abstract »    Full Text »    PDF »
Mesenchymal Stem Cells Cooperate with Bone Marrow Cells in Therapy of Diabetes.
V. S. Urban, J. Kiss, J. Kovacs, E. Gocza, V. Vas, E. Monostori, and F. Uher (2008)
Stem Cells 26, 244-253
   Abstract »    Full Text »    PDF »
Specific Inhibition of Autoimmune T Cell Transmigration Contributes to beta Cell Functionality and Insulin Synthesis in Non-obese Diabetic (NOD) Mice.
A. Y. Savinov, D. V. Rozanov, and A. Y. Strongin (2007)
J. Biol. Chem. 282, 32106-32111
   Abstract »    Full Text »    PDF »
Dual T Cell Receptor Expressing CD8+ T Cells with Tumor- and Self-Specificity Can Inhibit Tumor Growth without Causing Severe Autoimmunity.
M. Weinhold, D. Sommermeyer, W. Uckert, and T. Blankenstein (2007)
J. Immunol. 179, 5534-5542
   Abstract »    Full Text »    PDF »
Hematopoietic Stem Cells Derived From Adult Donors Are Not a Source of Pancreatic {beta}-Cells in Adult Nondiabetic Humans.
A. E. Butler, A. Huang, P. N. Rao, A. Bhushan, W. J. Hogan, R. A. Rizza, and P. C. Butler (2007)
Diabetes 56, 1810-1816
   Abstract »    Full Text »    PDF »
Autoimmunity and beta Cell Regeneration in Mouse and Human Type 1 Diabetes: The Peace Is Not Enough.
V. ABLAMUNITS, N. A. SHERRY, J. A. KUSHNER, and K. C. HEROLD (2007)
Ann. N.Y. Acad. Sci. 1103, 19-32
   Abstract »    Full Text »    PDF »
Elimination of insulitis and augmentation of islet beta cell regeneration via induction of chimerism in overtly diabetic NOD mice.
C. Zhang, I. Todorov, C.-L. Lin, M. Atkinson, F. Kandeel, S. Forman, and D. Zeng (2007)
PNAS 104, 2337-2342
   Abstract »    Full Text »    PDF »
Pancreas and beta-cell development: from the actual to the possible.
L. C. Murtaugh (2007)
Development 134, 427-438
   Abstract »    Full Text »    PDF »
Reversal of Type 1 Diabetes in Mice.
D. L. Faustman (2007)
N. Engl. J. Med. 356, 311-312
   Full Text »    PDF »
Recovery of Islet {beta}-Cell Function in Streptozotocin- Induced Diabetic Mice: An Indirect Role for the Spleen.
D. Yin, J. Tao, D. D. Lee, J. Shen, M. Hara, J. Lopez, A. Kuznetsov, L. H. Philipson, and A. S. Chong (2006)
Diabetes 55, 3256-3263
   Abstract »    Full Text »    PDF »
Comment on Papers by Chong et al., Nishio et al., and Suri et al. on Diabetes Reversal in NOD Mice.
D. L. Faustman, S. D. Tran, S. Kodama, B. M. Lodde, I. Szalayova, S. Key, Z. E. Toth, and E. Mezey (2006)
Science 314, 1243a
   Abstract »    Full Text »    PDF »
Response to Comment on Chong et al. on Diabetes Reversal in NOD Mice.
A. S. Chong, J. Shen, J. Tao, D. Yin, A. Kuznetsov, M. Hara, and L. H. Philipson (2006)
Science 314, 1243b
   Abstract »    Full Text »    PDF »
Response to Comment on Nishio et al. on Diabetes Reversal in NOD Mice.
J. Nishio, J. L. Gaglia, S. E. Turvey, C. Campbell, C. Benoist, and D. Mathis (2006)
Science 314, 1243c
   Abstract »    Full Text »    PDF »
Response to Comment on Suri et al. on Diabetes Reversal in NOD Mice.
A. Suri and E. R Unanue (2006)
Science 314, 1243d
   Abstract »    Full Text »    PDF »
Mechanistic insights into targeting T cell membrane proteinase to promote islet {beta}-cell rejuvenation in type 1 diabetes.
A. Y. Savinov, D. V. Rozanov, and A. Y. Strongin (2006)
FASEB J 20, 1793-1801
   Abstract »    Full Text »    PDF »
Reversal of type 1 diabetes in mice..
D. A. Melton (2006)
N. Engl. J. Med. 355, 89-90
   Full Text »    PDF »
Immunological reversal of autoimmune diabetes without hematopoietic replacement of beta cells..
A. Suri, B. Calderon, T. J. Esparza, K. Frederick, P. Bittner, and E. R. Unanue (2006)
Science 311, 1778-1780
   Abstract »    Full Text »    PDF »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)