Genes encoding tumor necrosis factor alpha and granzyme A are expressed during development of autoimmune diabetes.

Held, W; MacDonald, H R; Weissman, I L; Hess, M W; Mueller, C (1990). Genes encoding tumor necrosis factor alpha and granzyme A are expressed during development of autoimmune diabetes. Proceedings of the National Academy of Sciences of the United States of America - PNAS, 87(6), pp. 2239-2243. National Academy of Sciences NAS 10.1073/pnas.87.6.2239

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Progressive destruction of the insulin-producing beta cells in nonobese diabetic mice is observed after infiltration of the pancreas with lymphocytes [Makino, S., Kunimoto, K., Muraoka, Y., Mizushima, Y., Katagiri, K. & Tochino, Y. (1980) Exp. Anim. (Tokyo) 29, 1-13]. We show that the genes for tumor necrosis factor alpha and granzyme A, a serine protease associated with cytoplasmic granules of cytotoxic cells, are expressed during the development of spontaneous diabetes mellitus in the nonobese diabetic mouse. Granzyme A-positive cells are found both in and surrounding the islets, implying induction prior to islet infiltration. Tumor necrosis factor alpha expression is exclusively observed in the intra-islet infiltrate, predominantly in lymphocytes adjacent to insulin-producing beta cells, the targets of the autoimmune destruction, implying that tumor necrosis factor alpha expression is induced locally--i.e., in the islet. A considerable portion of cells expressing tumor necrosis factor alpha appear to be CD4+ T cells. This T-cell subset was previously shown to be necessary for development of the disease. Thus, these findings may be important for understanding the pathogenesis of autoimmune diabetes mellitus and potentially also for that of other T-cell-mediated autoimmune diseases.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Müller, Christoph (C)

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0027-8424

Publisher:

National Academy of Sciences NAS

Language:

English

Submitter:

Christoph Müller

Date Deposited:

21 Sep 2022 10:59

Last Modified:

29 Mar 2023 23:38

Publisher DOI:

10.1073/pnas.87.6.2239

PubMed ID:

2179951

BORIS DOI:

10.48350/172929

URI:

https://boris.unibe.ch/id/eprint/172929

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