Homeostatic and pathogenic role of renal dendritic cells.

Dendritic cells (DCs) form a bridge between the innate and adaptive immune systems and fundamentally have an impact on anti-infectious defense and immune-mediated diseases, including those affecting the kidney. The field of renal dendritic cells (rDCs) is rapidly evolving, and work in rodent models has provided the first insight into their functional role in kidney homeostasis and disease. Recent findings indicate that rDCs have an important sentinel role against kidney injury and infection. In acute immune-mediated disease they function in an anti-inflammatory manner, but may acquire pro-inflammatory functionality when renal inflammation becomes chronic. In chronic disease rDCs mature and stimulate rather than tolerize effector T cells, and may contribute to progression of kidney disease. Recent progress in aligning murine and human DC subsets has opened avenues for making knowledge obtained from mechanistic studies in animal models available for better interpretation of kidney biopsies. There is firsthand evidence indicating changes in human DC subsets and their distribution in some kidney diseases. Data are presently lacking on the identity of rDC progenitors, the molecular mechanisms governing their recruitment into the kidney, and the role of rDCs in kidney homeostasis. This review highlights recent findings in the study of rDCs.

Beta cells cannot directly prime diabetogenic CD8 T cells in nonobese diabetic mice.

Type 1 diabetes (T1D) is caused by the destruction of insulin-producing islet beta cells. CD8 T cells are prevalent in the islets of T1D patients and are the major effectors of beta cell destruction in nonobese diabetic (NOD) mice. In addition to their critical involvement in the late stages of diabetes, CD8 T cells are implicated in the initiation of disease. NOD mice, in which the beta2-microglobulin gene has been inactivated by gene targeting (NOD.beta2M-/-), have a deficiency in CD8 T cells and do not develop insulitis, which suggests that CD8 T cells are required for the initiation of T1D. However, neither in humans nor in NOD mice have the immunological requirements for diabetogenic CD8 T cells been precisely defined. In particular, it is not known in which cell type MHC class I expression is required for recruitment and activation of CD8 T cells. Here we have generated transgenic NOD mice, which lack MHC class I on mature professional antigen-presenting cells (pAPCs). These "class I APC-bald" mice developed periislet insulitis but not invasive intraislet insulitis, and they never became diabetic. Recruitment to the islet milieu does not therefore require cognate interaction between CD8 T cells and MHC class I on mature pAPCs. Conversely, such an interaction is critically essential to allow the crucial shift from periislet insulitis to invasive insulitis. Importantly, our findings demonstrate unequivocally that CD8 T cells cannot be primed to become diabetogenic by islet beta cells alone.