Diabetes, Vol 45, Issue 10 1350-1357, Copyright © 1996 by American Diabetes Association

ARTICLES

Both CD4+ and CD8+ T-cells in syngeneic islet grafts in NOD mice produce interferon-gamma during beta-cell destruction

W Suarez-Pinzon, RV Rajotte, TR Mosmann and A Rabinovitch
Department of Medicine, University of Alberta, Edmonton, Canada.

Syngeneic pancreatic islet grafts in diabetic NOD mice are infiltrated by mononuclear leukocytes, beta-cells are selectively destroyed, and autoimmune diabetes recurs. This model was used to identify islet graft-infiltrating mononuclear leukocytes associated with beta-cell destruction and diabetes recurrence. We compared cell surface antigen and cytokine-producing phenotypes of mononuclear leukocytes in islet grafts from NOD mice that were protected from diabetes recurrence by complete Freund's adjuvant (CFA) administration (beta-cell nondestructive insulitis) and in islet grafts from control phosphate-buffered saline (PBS)-injected NOD mice (beta-cell destructive insulitis). Islet grafts from CFA-injected mice contained fewer CD4+ and CD8+ cells and more B cells; also fewer interferon gamma (IFN-gamma), interleukin-2 (IL-2), and tumor necrosis factor alpha (TNF-alpha)-positive cells and more IL-4 and IL-10 positive cells. By performing two-color immunostaining of cell surface antigens and intracellular IFN-gamma, we found that IFN-gamma positive cells in islet grafts from CFA- and PBS-injected mice were approximately equally divided between CD4+ and CD8+ T-cell subsets. Also, the frequencies of both CD4+ IFN-gamma + and CD8+ IFN-gamma + cells were decreased in islet grafts from CFA-injected mice. These findings suggest that destruction of beta-cells in syngeneic islets transplanted into NOD mice is promoted by cells producing Th1-type cytokines (IFN-gamma, IL-2, and TNF-alpha) and prevented by cells producing TH2-type cytokines (IL-4 and IL-10). Furthermore, both CD4+ and CD8+ IFN-gamma-producing T-cells in the islet grafts appear to be involved in beta-cell destruction and diabetes recurrence.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. S. Narang and R. I. Mahato Biological and biomaterial approaches for improved islet transplantation. Pharmacol. Rev., June 1, 2006; 58(2): 194 - 243. [Abstract] [Full Text] [PDF]

				E Ludvigsen, M Stridsberg, E T Janson, and S Sandler Expression of somatostatin receptor subtypes 1-5 in pancreatic islets of normoglycaemic and diabetic NOD mice Eur. J. Endocrinol., September 1, 2005; 153(3): 445 - 454. [Abstract] [Full Text] [PDF]

				B. Kutlu, A. K. Cardozo, M. I. Darville, M. Kruhoffer, N. Magnusson, T. Orntoft, and D. L. Eizirik Discovery of Gene Networks Regulating Cytokine-Induced Dysfunction and Apoptosis in Insulin-Producing INS-1 Cells Diabetes, November 1, 2003; 52(11): 2701 - 2719. [Abstract] [Full Text] [PDF]

				W. L. Suarez-Pinzon, J. G. Mabley, R. Power, C. Szabo, and A. Rabinovitch Poly (ADP-Ribose) Polymerase Inhibition Prevents Spontaneous and Recurrent Autoimmune Diabetes in NOD Mice by Inducing Apoptosis of Islet-Infiltrating Leukocytes Diabetes, July 1, 2003; 52(7): 1683 - 1688. [Abstract] [Full Text] [PDF]

				W. Zhou, F. Zhang, and T. M. Aune Either IL-2 or IL-12 Is Sufficient to Direct Th1 Differentiation by Nonobese Diabetic T Cells J. Immunol., January 15, 2003; 170(2): 735 - 740. [Abstract] [Full Text] [PDF]

				A. Rabinovitch, W. L. Suarez-Pinzon, A.M. J. Shapiro, R. V. Rajotte, and R. Power Combination Therapy With Sirolimus and Interleukin-2 Prevents Spontaneous and Recurrent Autoimmune Diabetes in NOD Mice Diabetes, March 1, 2002; 51(3): 638 - 645. [Abstract] [Full Text] [PDF]

				M. E. Baldeon, T. Chun, and H. R. Gaskins Interferon-alpha and interferon-gamma differentially affect pancreatic beta -cell phenotype and function Am J Physiol Cell Physiol, July 1, 1998; 275(1): C25 - C32. [Abstract] [Full Text] [PDF]