Diabetes, Vol 37, Issue 2 252-255, Copyright © 1988 by American Diabetes Association

ARTICLES

NOD marrow stem cells adoptively transfer diabetes to resistant (NOD x NON)F1 mice

DV Serreze, EH Leiter, SM Worthen and LD Shultz
Jackson Laboratory, Bar Harbor, Maine 04609.

Autoimmune beta-cell destruction occurred in otherwise diabetes-resistant F1 mice from an outcross between the nonobese diabetic (NOD) and nonobese normal (NON) inbred strains after adoptive transfer of hematopoietic stem cells from NOD donors. F1 mice were lethally irradiated and reconstituted with either NOD, NON, or F1 bone marrow. Only F1 mice reconstituted with NOD bone marrow developed hyperglycemia. The long (greater than or equal to 16-wk) prodromal period required for expression of overt diabetes contrasted with the rapidity (4-6 days) with which kidney-grafted F1 or NON islets (but not anterior pituitary) were eliminated from diabetic F1 mice. Thus, development of beta-cell-specific immunologic effectors was a chronic process, but once sufficient levels of autoimmunity were achieved, implanted beta-cells could be eliminated in an acute fashion. Thus, expression of NOD diabetogenic alleles in hematopoietic progenitor cells is sufficient for development of anti-beta-cell immunity. The elimination of grafted NON islets shows the effectors are capable of eliminating beta-cells from mice without the diabetogenic genotype.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. E. Mathews, W. L. Suarez-Pinzon, J. J. Baust, K. Strynadka, E. H. Leiter, and A. Rabinovitch Mechanisms Underlying Resistance of Pancreatic Islets from ALR/Lt Mice to Cytokine-Induced Destruction J. Immunol., July 15, 2005; 175(2): 1248 - 1256. [Abstract] [Full Text] [PDF]

				D. J. Moore, H. Noorchashm, T. H. Lin, S. A. Greeley, and A. Naji NOD B-cells Are Insufficient to Incite T-Cell-Mediated Anti-islet Autoimmunity Diabetes, July 1, 2005; 54(7): 2019 - 2025. [Abstract] [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. J. Prasad and C. C. Goodnow Cell-intrinsic effects of non-MHC NOD genes on dendritic cell generation in vivo Int. Immunol., June 1, 2002; 14(6): 677 - 684. [Abstract] [Full Text] [PDF]

				M. Poulin and K. Haskins Induction of Diabetes in Nonobese Diabetic Mice by Th2 T Cell Clones from a TCR Transgenic Mouse J. Immunol., March 15, 2000; 164(6): 3072 - 3078. [Abstract] [Full Text] [PDF]

				D. V. Serreze, M. Bridgett, H. D. Chapman, E. Chen, S. D. Richard, and E. H. Leiter Subcongenic Analysis of the Idd13 Locus in NOD/Lt Mice: Evidence for Several Susceptibility Genes Including a Possible Diabetogenic Role for {beta}2-Microglobulin J. Immunol., February 1, 1998; 160(3): 1472 - 1478. [Abstract] [Full Text] [PDF]

				V. Thomas-Vaslin, D. Damotte, M. Coltey, N. M. Le Douarin, A. Coutinho, and J. Salaun Abnormal T cell selection on nod thymic epithelium is sufficient to induce autoimmune manifestations in C57BL/6 athymic nude mice PNAS, April 29, 1997; 94(9): 4598 - 4603. [Abstract] [Full Text] [PDF]

				K Haskins and M McDuffie Acceleration of diabetes in young NOD mice with a CD4+ islet-specific T cell clone Science, September 21, 1990; 249(4975): 1433 - 1436. [Abstract] [PDF]