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

Islet-specific T cells are essential in the development of type I diabetes. The role of non-lymphoid cells is relatively unclear, although infiltratio n of dendritic cells and macrophages is the first sign of islet autoimmunit y in diabetes-prone nonobese diabetic (NOD) mice. BDC2.5 is one of the auto reactive T cell clones isolated from NOD mice. Transfer of BDC2.5 T cells i nto young NOD mice accelerates diabetes development, whereas transgenic exp ression of the BDC2.5 T cell receptor on NOD T cells (BDC2.5 TCR-Tg NOD) ma rkedly reduces diabetes development. We show that, although the same antige n-specificity is involved, both models differ significantly in insulitis. B DC2.5 TCR-Tg NOD mice develop an extensive, but non-aggressive, peri-insuli tis by 3 weeks of age. In these large peri-islet infiltrates, resembling se condary lymphoid tissue, BM8(+) macrophages (M phi) are virtually absent. I n contrast, BDC2.5 T cell clone transfer results in an aggressive insulitis with small infiltrates, but relatively large numbers of BM8(+) M phi. Infi ltration 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 transfer red mice. ER-MP23(+) M phi are reduced in both transferred and transgenic m ice compared with wild-type NOD. Thus, this study underlines and extends pr evious data suggesting that M phi are implicated in both early and late pha ses in diabetes development. Furthermore, our data imply that subsets of no n-lymphoid cells have different roles in diabetes development. It is, there fore, important to recognize this heterogeneity when interpreting both in v ivo and in vitro studies concerning non-lymphoid cells in diabetes.