An Overview of the Immune System with Specific Reference to Membrane Encapsulation and Islet Transplantation

Abstract

The concept of immunoisolation by use of a bioartificial membrane is discussed, concentrating on the immunological mechanisms that are likely to be operative in the light of recent information on the workings of the immune system. Special attention is given to the use of encapsulation for the purpose of treating autoimmune diabetes by implantation of xenogeneic islet tissue. It is argued that the term immunoisolation is misleading because the immune system is always activated by the indirect pathway of antigen presentation and that the term immunomodulation would be more appropriate.

Causes of limited survival of microencapsulated pancreatic islet grafts

“…Local attraction of macrophages by shedding is more apparent for xenografts than for allografts, since virtually every protein shed by a xenograft is different from the host [52,54,55]. Xenogenic antigen release, especially the release of ␣-1,3-galactose, attracts and activates macrophages, which in turn release cytokines such as Il-1␤, TNF-␣, and IFN-␥, but also nitric oxide and oxygen radicals [54,56]. These macrophage-derived factors are small enough to pass the semipermeable membrane of microcapsules and may well affect encapsulated islet graft function and vitality.…”

Survival of encapsulated islets: More than a membrane story

“…This mechanism, however, has only a minor impact on encapsulated grafted cells because the membrane physically separates donor cells from recipient cells [26] . Humoral rejection does not require celltocell contact and is operable via mechanisms activated by the indirect recognition pathway.…”

Correction of Hyperglycemia in Type 1 Diabetic Models by Transplantation of Encapsulated Insulin-producing Cells Derived from Mouse Embryo Progenitor

“…Although alginate capsules can insulate cells from contact and attack by immune cells, immune reaction may still occur through humoral route by the release of cell debris (Calafiore et al 1997, Siebers et al 1997. It has been speculated that the failure of islet transplantation could be attributable to several factors including erforin, cytokines, nitric oxide, poor nutrition, and hypoxia (Siebers et al 1999, Gray 2001, de Groot et al 2003, 2004. Indeed, our study found that at least 12 cytokines were increased to different degrees in the peritoneal fluid of capsule-implanted mice.…”