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

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1993 Nov 1

PMID 8227346

Citations 126

Authors

N Itoh

T Hanafusa

A Miyazaki

J Miyagawa

K Yamagata

K Yamamoto

M Waguri

A Imagawa

S Tamura

M Inada

Affiliations

Soon will be listed here.

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

Makgoba M, Sanders M, Shaw S . The CD2-LFA-3 and LFA-1-ICAM pathways: relevance to T-cell recognition. Immunol Today. 1989; 10(12):417-22. DOI: 10.1016/0167-5699(89)90039-X. View

Yamagata K, Nakajima H, Hanafusa T, Noguchi T, Miyazaki A, Miyagawa J . Aspartic acid at position 57 of DQ beta chain does not protect against type 1 (insulin-dependent) diabetes mellitus in Japanese subjects. Diabetologia. 1989; 32(10):762-4. DOI: 10.1007/BF00274539. View

Springer T . Adhesion receptors of the immune system. Nature. 1990; 346(6283):425-34. DOI: 10.1038/346425a0. View

Hutchings P, Rosen H, OReilly L, Simpson E, Gordon S, Cooke A . Transfer of diabetes in mice prevented by blockade of adhesion-promoting receptor on macrophages. Nature. 1990; 348(6302):639-42. DOI: 10.1038/348639a0. View

Wang Y, Pontesilli O, Gill R, La Rosa F, Lafferty K . The role of CD4+ and CD8+ T cells in the destruction of islet grafts by spontaneously diabetic mice. Proc Natl Acad Sci U S A. 1991; 88(2):527-31. PMC: 50844. DOI: 10.1073/pnas.88.2.527. View

Zheng R, Abney E, Grubeck-Loebenstein B, Dayan C, Maini R, Feldmann M . Expression of intercellular adhesion molecule-1 and lymphocyte function-associated antigen-3 on human thyroid epithelial cells in Graves' and Hashimoto's diseases. J Autoimmun. 1990; 3(6):727-36. DOI: 10.1016/s0896-8411(05)80039-3. View

Vives M, Soldevila G, Alcalde L, Lorenzo C, Somoza N, Pujol-Borrell R . Adhesion molecules in human islet beta-cells. De novo induction of ICAM-1 but not LFA-3. Diabetes. 1991; 40(11):1382-90. DOI: 10.2337/diab.40.11.1382. View

Hayakawa M, Yokono K, Nagata M, Hatamori N, Ogawa W, Miki A . Morphological analysis of selective destruction of pancreatic beta-cells by cytotoxic T lymphocytes in NOD mice. Diabetes. 1991; 40(9):1210-7. DOI: 10.2337/diab.40.9.1210. View

Foulis A, McGill M, Farquharson M . Insulitis in type 1 (insulin-dependent) diabetes mellitus in man--macrophages, lymphocytes, and interferon-gamma containing cells. J Pathol. 1991; 165(2):97-103. DOI: 10.1002/path.1711650203. View

10.

Santamaria P, Nakhleh R, Sutherland D, Barbosa J . Characterization of T lymphocytes infiltrating human pancreas allograft affected by isletitis and recurrent diabetes. Diabetes. 1992; 41(1):53-61. DOI: 10.2337/diab.41.1.53. View

11.

Kay T, Campbell I, Oxbrow L, Harrison L . Overexpression of class I major histocompatibility complex accompanies insulitis in the non-obese diabetic mouse and is prevented by anti-interferon-gamma antibody. Diabetologia. 1991; 34(11):779-85. DOI: 10.1007/BF00408350. View

12.

Itoh N, Hanafusa T, Katsura H, Yamamoto K, Takeda A, Kurahashi A . Two types of autoantibodies to adrenal medullary cells in type 1 (insulin-dependent) diabetic patients: prevalence, properties and implications. J Autoimmun. 1991; 4(5):807-18. DOI: 10.1016/0896-8411(91)90175-c. View

13.

Itoh N, Hanafusa T, Miyagawa J, Tamura S, Inada M, Kawata S . Transthyretin (prealbumin) in the pancreas and sera of newly diagnosed type I (insulin-dependent) diabetic patients. J Clin Endocrinol Metab. 1992; 74(6):1372-7. DOI: 10.1210/jcem.74.6.1592883. View

14.

Hanninen A, Jalkanen S, Salmi M, Toikkanen S, Nikolakaros G, Simell O . Macrophages, T cell receptor usage, and endothelial cell activation in the pancreas at the onset of insulin-dependent diabetes mellitus. J Clin Invest. 1992; 90(5):1901-10. PMC: 443251. DOI: 10.1172/JCI116067. View

15.

Lampeter E, Kishimoto T, Rothlein R, Mainolfi E, Bertrams J, Kolb H . Elevated levels of circulating adhesion molecules in IDDM patients and in subjects at risk for IDDM. Diabetes. 1992; 41(12):1668-71. DOI: 10.2337/diab.41.12.1668. View

16.

Christianson S, Shultz L, Leiter E . Adoptive transfer of diabetes into immunodeficient NOD-scid/scid mice. Relative contributions of CD4+ and CD8+ T-cells from diabetic versus prediabetic NOD.NON-Thy-1a donors. Diabetes. 1993; 42(1):44-55. DOI: 10.2337/diab.42.1.44. View

17.

GEPTS W . Pathologic anatomy of the pancreas in juvenile diabetes mellitus. Diabetes. 1965; 14(10):619-33. DOI: 10.2337/diab.14.10.619. View

18.

Junker K, Egeberg J, Kromann H, Nerup J . An autopsy study of the islets of Langerhans in acute-onset juvenile diabetes mellitus. Acta Pathol Microbiol Scand A. 1977; 85(5):699-706. DOI: 10.1111/j.1699-0463.1977.tb00461.x. View

19.

Oschilewski U, Kiesel U, Kolb H . Administration of silica prevents diabetes in BB-rats. Diabetes. 1985; 34(2):197-9. DOI: 10.2337/diab.34.2.197. View

20.

Bottazzo G, Dean B, McNally J, MacKay E, Swift P, GAMBLE D . In situ characterization of autoimmune phenomena and expression of HLA molecules in the pancreas in diabetic insulitis. N Engl J Med. 1985; 313(6):353-60. DOI: 10.1056/NEJM198508083130604. View