Amelioration of immune-mediated experimental colitis: tolerance induction in the presence of pre-existing immunity and surrogate antigen bystander effect

ABSTRACT Oral tolerance is a recognized procedure for induction of antigen-specific peripheral immune hyporesponsiveness. Recently, it has been shown that oral tolerance can be used to prevent experimental colitis. The aim of this study was to test whether induction of oral tolerance toward proteins extracted from inflammatory and noninflammatory colons can alleviate preexisting experimental colitis. Colitis was induced in BALB/c mice by intracolonic instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS). Mice received five oral doses of colonic proteins extracted from TNBS-induced colitis or normal colons, before, or 7 days after colitis was induced. Standard clinical, macroscopic, and microscopic scores were used for colitis assessment. Serum interferon ␥ (IFN␥) and interleukin (IL)4 levels were measured by enzyme-linked immunosorbent assay. Feeding of colitis-or normal colon-extracted proteins before, or following colitis induction, ameliorated colonic inflammation as shown by decreased diarrhea, increased body weight, reduction of colonic ulcerations, intestinal and peritoneal adhesions, wall thickness, and edema. Histological parameters for colitis were markedly improved in tolerized animals, and there was a significant reduction in inflammatory response and mucosal ulcerations. Tolerized mice developed an increase in IL4 and a decrease in IFN␥ serum levels. The results show that induction of oral tolerance to colitis-or normal colon-extracted proteins down-regulated preexisting anticolon immune response, thereby ameliorating experimental colitis. Tolerance induction was mediated via a shift from a proinflammatory T helper (Th)1 to an anti-inflammatory Th2 immune response

Immunological Properties of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells

Summary: Age-related macular degeneration is caused by dysfunction and loss of retinal pigment epithelium (RPE) cells, and their transplantation may rescue visual functions and delay disease progression. Human embryonic stem cells (hESCs) may be an unlimited source of RPE cells for allotransplantation. We analyzed the immunomodulatory properties of hESC-derived RPE (hESC-RPE) cells, and showed that they inhibited T cell responses. Co-culture experiments showed that RPE cells inhibited interfon-γ secretion and proliferation of activated T cells. Furthermore, hESC-RPE cells enhanced T cell apoptosis and secretion of the anti-inflammatory cytokine interleukin-10 (IL-10). In addition, RPE cells altered the expression of T cell activation markers, CD69 and CD25. RPE cells transplanted into RCS rats without immunosuppression survived, provided retinal rescue, and enhanced IL-10 blood levels. Our data suggest that hESC-RPE cells have immunosuppressive properties. Further studies will determine if these properties are sufficient to alleviate the need for immunosuppression therapy after their clinical allotransplantation. : In this article, Reubinoff and colleagues describe the immunomodulatory properties of hESC-RPE cells. They show that the RPE cells inhibit IFN-γ secretion and proliferation of T cells and enhance T cells apoptosis and secretion of IL-10. In the absence of immunosuppression therapy, RPE cells survive, provide retinal rescue, and enhance IL-10 blood levels in a rat model of retinal degeneration. These findings are relevant to designing immunosuppressive regimens for RPE cell allotransplantation therapies. Keywords: retinal pigment epithelium, human embryonic stem cells, immunomodulation, immune-privileg