Antigen‐presenting cells in adoptively transferred and spontaneous autoimmune diabetes

Abstract

Histological techniques were used to identify antigen-presenting cells (APC) in adoptively transferred diabetes in NOD mice and Ins-HA transgenic mice, and in spontaneously diabetic NOD mice. In adoptively transferred disease, CD4+ T cells and F4/80+ macrophages dominated early infiltrates. By contrast, in spontaneously developing diabetes in NOD mice, lymphocytic infiltrates appeared to be well organized around a network of VCAM-1+ NLDC-145+ ICAM-1+ dendritic cells. Thus, the primary APC spontaneous autoimmune disease appears to be the strongly stimulatory dendritic cell rather than the normally resident macrophage. Next, we used chimeric animals to demonstrate that insulitis and diabetes could occur even when responding T cells were unable to recognize islet-specific antigen directly on beta cells. Altogether, the results demonstrate that immune-mediated damage does not require direct contact between CD4+ T cells and beta cells. Moreover, despite the induction of ICAM-1, VCAM-1, and class II on vascular endothelium near islet infiltrates, these experiments show that recruitment of lymphocytes occurs even when antigen presentation is not possible on vascular endothelium.

Immunohistochemical characterization of inflammatory cells and immunologic activation markers in muscle and nerve biopsy specimens from patients with systemic polyarteritis nodosa

“…Dendritic cells have a pivotal role in initiating the immune response, due to their antigen-presenting function and their ability to provide accessory signals for T cell activation (29,30). Dendritic cells have been identified in target tissues of several autoimmune diseases, including rheumatoid arthritis (3 l), primary biliary cirrhosis (32), inflammatory vasculopathy of chronic allograft rejection (33), giant cell arteritis (9), and experimental autoimmune diabetes (34). As observed in our samples, these cells are usually detected in incipient inflammatory infiltrates and become rare in well-established or scarring lesions (9,31,33).…”

Disproportionate Recruitment of CD8+ T Cells into the Central Nervous System by Professional Antigen-Presenting Cells

“…36 The mechanism by which CD8 ϩ T cells preferentially accumulated within the CNS is unclear, but the CNS itself must play a role shaping this response because initiation of CD4 ϩ T-cell responses does not lead to a disproportionate accumulation of CD8 ϩ T cells in other tissues. 37,38 For example, in our studies, a preferential accumulation of CD8 ϩ T cells was not observed when allogeneic dendritic cells were injected in the ear. Similarly, CD8 ϩ T cells accumulate only in relatively small numbers as compared with CD4 ϩ T cells during the initiation and progression of diabetes in a MHC-class-II-restricted TCR-transgenic model.…”

Pancreatic NOD beta cells express MHC class II protein and the frequency of I-Ag7 mRNA-expressing beta cells strongly increases during progression to autoimmune diabetes

“…Different groups have provided evidence that betacell destruction can occur in the complete absence of antigen-specific contact between T cells and pancreatic beta cells [40,41,42]. Nevertheless, the experimental approaches and models used in those reports do not rule out a direct presentation of autoantigens to selfreactive CD4+ T cells by the beta cells themselves as an essential step in the pathogenesis of diabetes in humans and NOD mice.…”