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American Society for Clinical Investigation Free PMC Article

J Clin Invest. 1993 Nov;92(5):2313-22. doi: 10.1172/JCI116835.

Mononuclear cell infiltration and its relation to the expression of major histocompatibility complex antigens and adhesion molecules in pancreas biopsy specimens from newly diagnosed insulin-dependent diabetes mellitus patients.

The Journal of clinical investigation

N Itoh, T Hanafusa, A Miyazaki, J Miyagawa, K Yamagata, K Yamamoto, M Waguri, A Imagawa, S Tamura, M Inada

Affiliations

  1. Second Department of Internal Medicine, Osaka University Medical School, Japan.

PMID: 8227346 PMCID: PMC288412 DOI: 10.1172/JCI116835
Free PMC Article

Abstract

We examined pancreas biopsy specimens from 18 newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients to elucidate the mechanism underlying beta cell destruction. Pancreas islets were seen in all patients and insulitis in eight patients. Infiltrating mononuclear cells consisted of CD4+T, CD8+T, B lymphocytes, and macrophages. Among them, CD8+T lymphocytes were predominant and macrophages followed. The expression of MHC class I antigens was increased in islet and endothelial cells in nine patients. MHC class II expression was increased in endothelial cells of the same patients. The expression of intercellular adhesion molecule-1 was increased in endothelial cells in two of the nine patients with MHC hyperexpression; in one of them, lymphocyte function-associated antigen-3 expression was also increased. Out of the eight patients with insulitis, seven showed MHC class I hyper-expression, whereas 2 of the 10 patients without insulitis showed the phenomenon (P < 0.05). The relation between insulitis and the hyperexpression of adhesion molecules was not evident. In conclusion, we revealed the close relation between CD8+T lymphocyte-predominant insulitis and MHC class I hyperexpression in islet cells. This suggests that infiltrating CD8+T lymphocytes recognize islet autoantigens in association with increased MHC class I molecules and act as major effector cells in autoimmune response against islet cells in IDDM pancreases. The role of adhesion molecules in the pathogenesis of IDDM still remains to be elucidated.

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References

  1. Immunol Today. 1989 Dec;10(12):417-22 - PubMed
  2. Diabetologia. 1989 Oct;32(10):762-4 - PubMed
  3. Nature. 1990 Aug 2;346(6283):425-34 - PubMed
  4. Nature. 1990 Dec 13;348(6302):639-42 - PubMed
  5. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):527-31 - PubMed
  6. J Autoimmun. 1990 Dec;3(6):727-36 - PubMed
  7. Diabetes. 1991 Nov;40(11):1382-90 - PubMed
  8. Diabetes. 1991 Sep;40(9):1210-7 - PubMed
  9. J Pathol. 1991 Oct;165(2):97-103 - PubMed
  10. Diabetes. 1992 Jan;41(1):53-61 - PubMed
  11. Diabetologia. 1991 Nov;34(11):779-85 - PubMed
  12. J Autoimmun. 1991 Oct;4(5):807-18 - PubMed
  13. J Clin Endocrinol Metab. 1992 Jun;74(6):1372-7 - PubMed
  14. J Clin Invest. 1992 Nov;90(5):1901-10 - PubMed
  15. Diabetes. 1992 Dec;41(12):1668-71 - PubMed
  16. Diabetes. 1993 Jan;42(1):44-55 - PubMed
  17. Diabetes. 1965 Oct;14(10):619-33 - PubMed
  18. Acta Pathol Microbiol Scand A. 1977 Sep;85(5):699-706 - PubMed
  19. Diabetes. 1985 Feb;34(2):197-9 - PubMed
  20. N Engl J Med. 1985 Aug 8;313(6):353-60 - PubMed
  21. Lab Invest. 1985 Aug;53(2):132-44 - PubMed
  22. Diabetologia. 1986 May;29(5):267-74 - PubMed
  23. Diabetes. 1986 Nov;35(11):1215-24 - PubMed
  24. Nature. 1986 Sep 18-24;323(6085):262-4 - PubMed
  25. Clin Exp Immunol. 1986 Jul;65(1):128-39 - PubMed
  26. Diabetes. 1987 Apr;36(4):510-7 - PubMed
  27. Diabetologia. 1987 May;30(5):333-43 - PubMed
  28. J Exp Med. 1987 Oct 1;166(4):823-32 - PubMed
  29. J Immunol. 1988 Jan 1;140(1):52-8 - PubMed
  30. Lancet. 1987 Dec 19;2(8573):1423-7 - PubMed
  31. Diabetes. 1988 Jul;37(7):989-91 - PubMed
  32. Arthritis Rheum. 1989 Jan;32(1):22-30 - PubMed
  33. Annu Rev Immunol. 1989;7:601-24 - PubMed
  34. Proc Natl Acad Sci U S A. 1989 Jun;86(11):4282-6 - PubMed
  35. Eur J Immunol. 1989 Oct;19(10):1947-51 - PubMed
  36. Diabetologia. 1990 Feb;33(2):105-11 - PubMed

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