Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1987 Oct 1;166(4):823–832. doi: 10.1084/jem.166.4.823

Syngeneic transfer of autoimmune diabetes from diabetic NOD mice to healthy neonates. Requirement for both L3T4+ and Lyt-2+ T cells

PMCID: PMC2188705  PMID: 3309126

Abstract

We have developed a model of syngeneic adoptive transfer for type I diabetes mellitus of NOD mice. This model consists in injecting spleen cells from diabetic adult mice into newborn NOD recipients. 50% of recipients inoculated with 20 X 10(6) cells develop diabetes within the first 10 wk of life, at a time when none of the control littermates have yet become diabetic. The earliest successful transfers are observed at 3 wk of age, at a time when controls do not even exhibit histological changes in their pancreas. In addition we have shown that: (a) both males and females can be adoptively transferred, despite the fact that males rarely develop spontaneous diabetes in our colony; (b) diabetes transfer is a dose-dependent phenomenon that provides an in vivo assay for comparing the autoimmune potential of spleen cells from mice at various stages of their natural history; (c) the susceptibility of the recipients to the transfer is limited in time and declines after 3 wk; and (d) both L3T4+ and Lyt-2+ T cell subsets are necessary for the successful transfer. The neonatal syngeneic transfer provides an effective model for studies of the cellular events involved at regulatory and effector stages of autoimmune type I diabetes.

Full Text

The Full Text of this article is available as a PDF (688.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adams T. E., Alpert S., Hanahan D. Non-tolerance and autoantibodies to a transgenic self antigen expressed in pancreatic beta cells. Nature. 1987 Jan 15;325(6101):223–228. doi: 10.1038/325223a0. [DOI] [PubMed] [Google Scholar]
  2. Bendtzen K., Mandrup-Poulsen T., Nerup J., Nielsen J. H., Dinarello C. A., Svenson M. Cytotoxicity of human pI 7 interleukin-1 for pancreatic islets of Langerhans. Science. 1986 Jun 20;232(4757):1545–1547. doi: 10.1126/science.3086977. [DOI] [PubMed] [Google Scholar]
  3. Boitard C., Bach J. F. Cell-mediated versus humoral immunity in autoimmune diseases and their pharmacologic control with particular reference to type I diabetes mellitus. Concepts Immunopathol. 1986;3:193–224. [PubMed] [Google Scholar]
  4. Boitard C., Chatenoud L. M., Debray-Sachs M. In vitro inhibition of pancreatic B cell function by lymphocytes from diabetics with associated autoimmune diseases: a T cell phenomenon. J Immunol. 1982 Dec;129(6):2529–2531. [PubMed] [Google Scholar]
  5. Dialynas D. P., Quan Z. S., Wall K. A., Pierres A., Quintáns J., Loken M. R., Pierres M., Fitch F. W. Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK1.5: similarity of L3T4 to the human Leu-3/T4 molecule. J Immunol. 1983 Nov;131(5):2445–2451. [PubMed] [Google Scholar]
  6. Gepts W. Pathologic anatomy of the pancreas in juvenile diabetes mellitus. Diabetes. 1965 Oct;14(10):619–633. doi: 10.2337/diab.14.10.619. [DOI] [PubMed] [Google Scholar]
  7. Golding H., Munitz T. I., Singer A. Characterization of antigen-specific, Ia-restricted, L3T4+ cytolytic T lymphocytes and assessment of thymic influence on their self specificity. J Exp Med. 1985 Sep 1;162(3):943–961. doi: 10.1084/jem.162.3.943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Goverman J., Hunkapiller T., Hood L. A speculative view of the multicomponent nature of T cell antigen recognition. Cell. 1986 May 23;45(4):475–484. doi: 10.1016/0092-8674(86)90279-5. [DOI] [PubMed] [Google Scholar]
  9. Harada M., Makino S. Promotion of spontaneous diabetes in non-obese diabetes-prone mice by cyclophosphamide. Diabetologia. 1984 Dec;27(6):604–606. doi: 10.1007/BF00276978. [DOI] [PubMed] [Google Scholar]
  10. Hattori M., Buse J. B., Jackson R. A., Glimcher L., Dorf M. E., Minami M., Makino S., Moriwaki K., Kuzuya H., Imura H. The NOD mouse: recessive diabetogenic gene in the major histocompatibility complex. Science. 1986 Feb 14;231(4739):733–735. doi: 10.1126/science.3003909. [DOI] [PubMed] [Google Scholar]
  11. Ikehara S., Ohtsuki H., Good R. A., Asamoto H., Nakamura T., Sekita K., Muso E., Tochino Y., Ida T., Kuzuya H. Prevention of type I diabetes in nonobese diabetic mice by allogenic bone marrow transplantation. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7743–7747. doi: 10.1073/pnas.82.22.7743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ledbetter J. A., Herzenberg L. A. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63–90. doi: 10.1111/j.1600-065x.1979.tb00289.x. [DOI] [PubMed] [Google Scholar]
  13. Like A. A., Weringer E. J., Holdash A., McGill P., Atkinson D., Rossini A. A. Adoptive transfer of autoimmune diabetes mellitus in biobreeding/Worcester (BB/W) inbred and hybrid rats. J Immunol. 1985 Mar;134(3):1583–1587. [PubMed] [Google Scholar]
  14. Makino S., Kunimoto K., Muraoka Y., Katagiri K. Effect of castration on the appearance of diabetes in NOD mouse. Jikken Dobutsu. 1981 Apr;30(2):137–140. doi: 10.1538/expanim1978.30.2_137. [DOI] [PubMed] [Google Scholar]
  15. McGrath M. S., Pillemer E., Weissman I. L. Murine leukaemogenesis: monoclonal antibodies to T-cell determinants arrest T-lymphoma cell proliferation. Nature. 1980 May 22;285(5762):259–261. doi: 10.1038/285259a0. [DOI] [PubMed] [Google Scholar]
  16. Miyazaki A., Hanafusa T., Yamada K., Miyagawa J., Fujino-Kurihara H., Nakajima H., Nonaka K., Tarui S. Predominance of T lymphocytes in pancreatic islets and spleen of pre-diabetic non-obese diabetic (NOD) mice: a longitudinal study. Clin Exp Immunol. 1985 Jun;60(3):622–630. [PMC free article] [PubMed] [Google Scholar]
  17. Ohneda A., Kobayashi T., Nihei J., Tochino Y., Kanaya H., Makino S. Insulin and glucagon in spontaneously diabetic non-obese mice. Diabetologia. 1984 Oct;27(4):460–463. doi: 10.1007/BF00273911. [DOI] [PubMed] [Google Scholar]
  18. Portha B., Levacher C., Picon L., Rosselin G. Diabetogenic effect of streptozotocin in the rat during the perinatal period. Diabetes. 1974 Nov;23(11):889–895. doi: 10.2337/diab.23.11.889. [DOI] [PubMed] [Google Scholar]
  19. Sarmiento M., Glasebrook A. L., Fitch F. W. IgG or IgM monoclonal antibodies reactive with different determinants on the molecular complex bearing Lyt 2 antigen block T cell-mediated cytolysis in the absence of complement. J Immunol. 1980 Dec;125(6):2665–2672. [PubMed] [Google Scholar]
  20. Wicker L. S., Miller B. J., Mullen Y. Transfer of autoimmune diabetes mellitus with splenocytes from nonobese diabetic (NOD) mice. Diabetes. 1986 Aug;35(8):855–860. doi: 10.2337/diab.35.8.855. [DOI] [PubMed] [Google Scholar]
  21. Yokono K., Shii K., Hari J., Yaso S., Imamura Y., Ejiri K., Ishihara K., Fujii S., Kazumi T., Taniguchi H. Production of monoclonal antibodies to islet cell surface antigens using hybridization of spleen lymphocytes from non-obese diabetic mice. Diabetologia. 1984 May;26(5):379–385. doi: 10.1007/BF00266041. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES