Immune Cell Populations in Nonhuman Primate Islets

Abstract

Islet transplantation is a promising cellular therapy for the treatment of type 1 diabetes (T1D). The immunogenicity of isolated islets has been of interest to the transplant community for many years, as upon transplantation, islets are damaged or destroyed through specific and nonspecific inflammatory and immune events. Antigen presenting cells (APC) are crucial intermediates in the generation of both innate and specific immune responses, and it has long been understood that some APC are resident in islets in situ, as well as after isolation. Our aim was to identify and characterize intraislet resident populations of APC and other immune cells in islets from nonhuman primates ( Macaca fascicularis) in situ (pancreas biopsies obtained prerecovery) and after isolation using immunohistochemistry, confocal microscopy, and flow cytometry. The numbers of cells obtained in situ are similar to those in islets postisolation. Each isolated islet equivalent contains an average of 21.8 immune cells, 14.7 (67%) of which are APC. Many of these APC are dentritic cells and, surprisingly, 50% are B lymphocytes. The number of islet-resident immune cells increases with islet size, with greater numbers in large versus small islets ( p < 0.001). The APC were localized around the exterior or spread evenly throughout the islets, with no definitive orientation identified. This knowledge will be useful to develop tailored modulation strategies to decrease immunogenicity, enhance engraftment, and ultimately prevent islet rejection.