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

JGM Rosmalen, T Martin, C Dobbs, JSA Voerman, HA Drexhage, K Haskins, PJM Leenen

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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 (M phi) 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(+) M phi. Infiltration of BM8(+) M phi therefore correlates with islet destruction. This is, however, not observed for all M phi; Monts-4(+) M phi follow a reverse pattern and are present in higher numbers in BDC2.5 TCR-Tg than in transferred mice. ER-MP23(+) M phi are reduced in both transferred and transgenic mice compared with wild-type NOD. Thus, this study underlines and extends previous data suggesting that M phi 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.

Original languageEnglish
Pages (from-to)23-30
Number of pages8
JournalLaboratory Investigation
Volume80
Issue number1
Publication statusPublished - Jan-2000
Externally publishedYes

Keywords

  • CD4(+) T-CELLS
  • NOD MICE
  • ANTIGEN
  • INITIATION
  • PATHOGENESIS
  • INSULITIS
  • MELLITUS
  • CLONES

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