The Journal of Immunology, Vol 159, Issue 4 1599-1603, Copyright © 1997 by American Association of Immunologists

ARTICLES

IL-4 expression by grafts from transgenic mice fails to prevent allograft rejection

R Mueller, JD Davies, T Krahl and N Sarvetnick
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Cell-mediated tissue destruction, such as that occurring in allograft rejection, is thought to be mediated by Th1 cells and cytokines. We have recently shown that transgenic expression of the Th2 cytokine IL-4 by pancreatic beta cells completely protects nonobese diabetic (NOD) mice from autoimmune diabetes by inducing functional tolerance among autoreactive T cells. To investigate whether local IL-4 production could also induce functional tolerance among alloreactive T cells and thus prevent allograft rejection, we transplanted pancreata from transgenic neonatal mice and their nontransgenic littermates into allogeneic hosts. Within 2 wk, recipient mice had rejected their grafts regardless of the transgene's presence or absence. Considering that the vigorous immune response induced might have prevented any effect by IL- 4, we injected recipient mice with anti-CD4 and anti-CD8 mAbs, thereby depleting them of T cells and thus providing the islets with an opportunity to mature and grow. This approach indeed delayed rejection of neonatal pancreata from nontransgenic mice by >1 wk. By that time, however, pancreata from transgenic mice had also been rejected. Our results indicate that the allograft rejection response under these conditions, in contrast to the autoimmune response in NOD mice, cannot be regulated by local IL-4 production, regardless of the cytokine's impact on Th1 cells.

This article has been cited by other articles:

				P. Zhou, G. L. Szot, Z. Guo, O. Kim, G. He, J. Wang, M. J. Grusby, K. A. Newell, J. R. Thistlethwaite, J. A. Bluestone, et al. Role of STAT4 and STAT6 Signaling in Allograft Rejection and CTLA4-Ig-Mediated Tolerance J. Immunol., November 15, 2000; 165(10): 5580 - 5587. [Abstract] [Full Text] [PDF]

				Y. Furukawa, D. A. Mandelbrot, P. Libby, A. H. Sharpe, and R. N. Mitchell Association of B7-1 Co-Stimulation with the Development of Graft Arterial Disease : Studies Using Mice Lacking B7-1, B7-2, or B7-1/B7-2 Am. J. Pathol., August 1, 2000; 157(2): 473 - 484. [Abstract] [Full Text] [PDF]

				J. D. Davies, E. O'Connor, D. Hall, T. Krahl, J. Trotter, and N. Sarvetnick CD4+ CD45RB Low-Density Cells from Untreated Mice Prevent Acute Allograft Rejection J. Immunol., November 15, 1999; 163(10): 5353 - 5357. [Abstract] [Full Text] [PDF]

				S. T. Azar, H. Tamim, H. N. Beyhum, M. Z. Habbal, and W. Y. Almawi Type I (Insulin-Dependent) Diabetes Is a Th1- and Th2-Mediated Autoimmune Disease Clin. Vaccine Immunol., May 1, 1999; 6(3): 306 - 310. [Full Text] [PDF]

				W. Y. Almawi, H. Tamim, and S. T. Azar T Helper Type 1 and 2 Cytokines Mediate the Onset and Progression of Type I (Insulin-Dependent) Diabetes J. Clin. Endocrinol. Metab., May 1, 1999; 84(5): 1497 - 1502. [Abstract] [Full Text]

				B. Balasa, C. Deng, J. Lee, P. Christadoss, and N. Sarvetnick The Th2 Cytokine IL-4 Is Not Required for the Progression of Antibody-Dependent Autoimmune Myasthenia Gravis J. Immunol., September 15, 1998; 161(6): 2856 - 2862. [Abstract] [Full Text] [PDF]

				X. C. Li, M. S. Zand, Y. Li, X. X. Zheng, and T. B. Strom On Histocompatibility Barriers, Th1 to Th2 Immune Deviation, and the Nature of the Allograft Responses J. Immunol., September 1, 1998; 161(5): 2241 - 2247. [Abstract] [Full Text] [PDF]

				P. L. Mottram, A. Raisanen-Sokolowski, T. Glysing-Jensen, A. N. Stein-Oakley, and M. E. Russell2 Cardiac Allografts from IL-4 Knockout Recipients: Assessment of Transplant Arteriosclerosis and Peripheral Tolerance J. Immunol., July 15, 1998; 161(2): 602 - 609. [Abstract] [Full Text] [PDF]

				X. C. Li, P. Roy-Chaudhury, W. W. Hancock, R. Manfro, M. S. Zand, Y. Li, X. X. Zheng, P. W. Nickerson, J. Steiger, T. R. Malek, et al. IL-2 and IL-4 Double Knockout Mice Reject Islet Allografts: A Role for Novel T Cell Growth Factors in Allograft Rejection J. Immunol., July 15, 1998; 161(2): 890 - 896. [Abstract] [Full Text] [PDF]