Diabetes, Vol 38, Issue 7 894-901, Copyright © 1989 by American Diabetes Association

ARTICLES

Reciprocal allogeneic bone marrow transplantation between NOD mice and diabetes-nonsusceptible mice associated with transfer and prevention of autoimmune diabetes

DM LaFace and AB Peck
Department of Pathology, College of Medicine, University of Florida, Gainesville.

Reciprocal allogeneic bone marrow transplantations were carried out between diabetes-susceptible nonobese diabetic (NOD) and diabetes-nonsusceptible C57BL/6 or B10.BR/cd mice to examine the role of the immune system and host environment in the development of autoimmune diabetes. Serotyping of lethally irradiated hosts reconstituted with allogeneic bone marrow showed the hematopoietically derived cells to be of donor origin. Our results showed that lethally irradiated NOD mice reconstituted with a B10.BR/cd hematopoietic cell system remained totally free of insulitis, failed to develop diabetes, and thrived to old age. In contrast, lethally irradiated C57BL/6 or B10.BR/cd mice reconstituted with an NOD hematopoietic cell system all developed insulitis, but only approximately 10% progressed to overt diabetes. Direct adoptive transfer of insulitis and diabetes by mature T-lymphocytes apparently was not required; analogous results were obtained when diabetes-nonsusceptible hosts were reconstituted with NOD hematopoietic cells containing T-lymphocytes or devoid of Thy-1+ cells. The difference in frequency for the development of insulitis versus insulitis plus overt diabetes in C57BL/6 and B10.BR/cd mice suggests that the hematopoietically derived immune cells from NOD mice were sufficient to induce anti-islet reactivity but may require the diabetogenic host environment to develop the frequency and severity of diabetes observed in NOD mice.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H. S. Li, D. L. Ligons, N. R. Rose, and M. L. Guler Genetic Differences in Bone Marrow-Derived Lymphoid Lineages Control Susceptibility to Experimental Autoimmune Myocarditis J. Immunol., June 1, 2008; 180(11): 7480 - 7484. [Abstract] [Full Text] [PDF]

				L. Verda, D. A. Kim, S. Ikehara, L. Statkute, D. Bronesky, Y. Petrenko, Y. Oyama, X. He, C. Link, N. N. Vahanian, et al. Hematopoietic Mixed Chimerism Derived from Allogeneic Embryonic Stem Cells Prevents Autoimmune Diabetes Mellitus in NOD Mice Stem Cells, February 1, 2008; 26(2): 381 - 386. [Abstract] [Full Text] [PDF]

				Y.-G. Chen, P. A. Silveira, M. A. Osborne, H. D. Chapman, and D. V. Serreze Cellular Expression Requirements for Inhibition of Type 1 Diabetes by a Dominantly Protective Major Histocompatibility Complex Haplotype Diabetes, February 1, 2007; 56(2): 424 - 430. [Abstract] [Full Text] [PDF]

				G. F. Beilhack, R. R. Landa, M. A. Masek, and J. A. Shizuru Prevention of Type 1 Diabetes with Major Histocompatibility Complex-Compatible and Nonmarrow Ablative Hematopoietic Stem Cell Transplants Diabetes, June 1, 2005; 54(6): 1770 - 1779. [Abstract] [Full Text] [PDF]

				P. M. Chilton, F. Rezzoug, M. Z. Ratajczak, I. Fugier-Vivier, J. Ratajczak, M. Kucia, Y. Huang, M. K. Tanner, and S. T. Ildstad Hematopoietic stem cells from NOD mice exhibit autonomous behavior and a competitive advantage in allogeneic recipients Blood, March 1, 2005; 105(5): 2189 - 2197. [Abstract] [Full Text] [PDF]

				B. Nikolic, Y. Takeuchi, I. Leykin, Y. Fudaba, R. N. Smith, and M. Sykes Mixed Hematopoietic Chimerism Allows Cure of Autoimmune Diabetes Through Allogeneic Tolerance and Reversal of Autoimmunity Diabetes, February 1, 2004; 53(2): 376 - 383. [Abstract] [Full Text]

				C. Ricordi Lilly Lecture 2002: Islet Transplantation: A Brave New World Diabetes, July 1, 2003; 52(7): 1595 - 1603. [Full Text] [PDF]

				G. F. Beilhack, Y. C. Scheffold, I. L. Weissman, C. Taylor, L. Jerabek, M. J. Burge, M. A. Masek, and J. A. Shizuru Purified Allogeneic Hematopoietic Stem Cell Transplantation Blocks Diabetes Pathogenesis in NOD Mice Diabetes, January 1, 2003; 52(1): 59 - 68. [Abstract] [Full Text] [PDF]

				D. W. van Bekkum Experimental basis of hematopoietic stem cell transplantation for treatment of autoimmune diseases J. Leukoc. Biol., October 1, 2002; 72(4): 609 - 620. [Abstract] [Full Text] [PDF]

				S. Thiessen, P. Serra, A. Amrani, J. Verdaguer, and P. Santamaria T-Cell Tolerance by Dendritic Cells and Macrophages as a Mechanism for the Major Histocompatibility Complex-Linked Resistance to Autoimmune Diabetes Diabetes, February 1, 2002; 51(2): 325 - 338. [Abstract] [Full Text] [PDF]

				R. K. Burt, S. Slavin, W. H. Burns, and A. M. Marmont Induction of tolerance in autoimmune diseases by hematopoietic stem cell transplantation: getting closer to a cure? Blood, February 1, 2002; 99(3): 768 - 784. [Abstract] [Full Text] [PDF]

				D. Schmidt, J. Verdaguer, N. Averill, and P. Santamaria A Mechanism for the Major Histocompatibility Complex-linked Resistance to Autoimmunity J. Exp. Med., October 6, 1997; 186(7): 1059 - 1075. [Abstract] [Full Text] [PDF]