Breaking of Oral Tolerance by an Encapsulated Antigen

Flanagan, Michael; Jain, Shilpa L.; Michael, J. Gabriel

doi:10.1111/j.1749-6632.1996.tb21147.x

Cited by 13 publications

(7 citation statements)

References 3 publications

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“…One way to confirm a causative link between gut immunity and our ability to transplant E28 pig pancreatic primordia and porcine islets in non-immune-suppressed hosts would be to “break” the established oral tolerance [38], using glucose control as a readout in the rat mode, theoretically possible so long as extrathymic deletion of antigen-reactive T cells [35] has not occurred. …”

Section: Discussionmentioning

confidence: 99%

Engraftment of Insulin-Producing Cells from Porcine Islets in Non-Immune-Suppressed Rats or Nonhuman Primates Transplanted Previously with Embryonic Pig Pancreas

Hammerman

2011

Journal of Transplantation

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Transplantation therapy for diabetes is limited by unavailability of donor organs and outcomes complicated by immunosuppressive drug toxicity. Xenotransplantation is a strategy to overcome supply problems. Implantation of tissue obtained early during embryogenesis is a way to reduce transplant immunogenicity. Insulin-producing cells originating from embryonic pig pancreas obtained very early following pancreatic primordium formation (embryonic day 28 (E28)) engraft long-term in non-immune, suppressed diabetic rats or rhesus macaques. Morphologically, similar cells originating from adult porcine islets of Langerhans (islets) engraft in non-immune-suppressed rats or rhesus macaques previously transplanted with E28 pig pancreatic primordia. Our data are consistent with induction of tolerance to an endocrine cell component of porcine islets induced by previous transplantation of embryonic pig pancreas, a novel finding we designate organogenetic tolerance. The potential exists for its use to enable the use of pigs as islet cell donors for humans with no immune suppression requirement.

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Section: Discussionmentioning

confidence: 99%

Engraftment of Insulin-Producing Cells from Porcine Islets in Non-Immune-Suppressed Rats or Nonhuman Primates Transplanted Previously with Embryonic Pig Pancreas

Hammerman

2011

Journal of Transplantation

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“…Recently developed techniques of antigen delivery in the gastrointestinal tract by coupling with cholera toxin B subunit or micro-encapsulation (20) are potentially able to modify this situation.…”

mentioning

confidence: 99%

Interruption of recently induced immune responses by oral administration of antigen

Condé

Stransky

Faria

et al. 1998

Braz J Med Biol Res

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Interest in oral tolerance has been renewed in the last few years as a possibility of intervention in human autoimmune diseases. An obstacle in this direction is that, although easily induced in animals virgin of contact with the antigen, oral tolerance becomes hard to induce in previously immunized animals. The present results show that there is an early period after primary immunization in which prolonged oral exposure to the antigen may arrest ongoing immune responses. Beyond this period, oral exposures to the antigen become ineffective and may actually boost immune responses. The end of the susceptible period coincides with the emergence of free specific antibodies in serum. However, the previous administration of purified anti-ovalbumin antibodies (40 µg) was unable to block the induction of oral tolerance to ovalbumin in normal mice.

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“…Studies have demonstrated that mice fed encapsulated protein had greater capacity to suppress specific serum IgG than soluble protein, but if the encapsulated dose was too high, oral tolerance was broken and a strong, Th2 cell response was activated. 24,25 In 2000, Pecquet et al 26 demonstrated that the oral administration of PLGA microspheres loaded with beta-lactoglobulin were able to induce oral tolerance in mice at a dose 10,000 times less than required with soluble antigen.…”

Section: Discussionmentioning

confidence: 98%

Desensitizing mice to ovalbumin through subcutaneous microsphere immunotherapy (SMITH)

Reisacher

Liotta

Yazdi

et al. 2011

Int Forum Allergy Rhinol

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Breaking of Oral Tolerance by an Encapsulated Antigen

Cited by 13 publications

References 3 publications

Engraftment of Insulin-Producing Cells from Porcine Islets in Non-Immune-Suppressed Rats or Nonhuman Primates Transplanted Previously with Embryonic Pig Pancreas

Engraftment of Insulin-Producing Cells from Porcine Islets in Non-Immune-Suppressed Rats or Nonhuman Primates Transplanted Previously with Embryonic Pig Pancreas

Interruption of recently induced immune responses by oral administration of antigen

Desensitizing mice to ovalbumin through subcutaneous microsphere immunotherapy (SMITH)

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