Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2000 Jan;80(1):23-30.
doi: 10.1038/labinvest.3780004.

Subsets of macrophages and dendritic cells in nonobese diabetic mouse pancreatic inflammatory infiltrates: correlation with the development of diabetes

J G Rosmalen  1 , T Martin, C Dobbs, J S Voerman, H A Drexhage, K Haskins, P J Leenen
Affiliations
Free article

Subsets of macrophages and dendritic cells in nonobese diabetic mouse pancreatic inflammatory infiltrates: correlation with the development of diabetes

J G Rosmalen et al. Lab Invest. 2000 Jan.
Free article

Abstract

Islet-specific T cells are essential in the development of type I diabetes. The role of non-lymphoid cells is relatively unclear, although infiltration of dendritic cells and macrophages is the first sign of islet autoimmunity in diabetes-prone nonobese diabetic (NOD) mice. BDC2.5 is one of the autoreactive T cell clones isolated from NOD mice. Transfer of BDC2.5 T cells into young NOD mice accelerates diabetes development, whereas transgenic expression of the BDC2.5 T cell receptor on NOD T cells (BDC2.5 TCR-Tg NOD) markedly reduces diabetes development. We show that, although the same antigen-specificity is involved, both models differ significantly in insulitis. BDC2.5 TCR-Tg NOD mice develop an extensive, but non-aggressive, peri-insulitis by 3 weeks of age. In these large peri-islet infiltrates, resembling secondary lymphoid tissue, BM8+ macrophages (Mphi) are virtually absent. In contrast, BDC2.5 T cell clone transfer results in an aggressive insulitis with small infiltrates, but relatively large numbers of BM8 Mphi. Infiltration of BM8+ Mphi therefore correlates with islet destruction. This is, however, not observed for all Mphi; Monts-4+ Mphi follow a reverse pattern and are present in higher numbers in BDC2.5 TCR-Tg than in transferred mice. ER-MP23+ Mphi are reduced in both transferred and transgenic mice compared with wild-type NOD. Thus, this study underlines and extends previous data suggesting that Mphi are implicated in both early and late phases in diabetes development. Furthermore, our data imply that subsets of non-lymphoid cells have different roles in diabetes development. It is, therefore, important to recognize this heterogeneity when interpreting both in vivo and in vitro studies concerning non-lymphoid cells in diabetes.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types