Induction of Autoimmune Diabetes by Oral Administration of Autoantigen
SciencePublished 6 December 1996
Effrossini Blanas, Federico Carbone, Janette Allison, J. F. A. P. Miller, William R. Heath
Citations259
SJR quartileQ1
SJR score10.42
SNIP6.62
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
Oral administration of autoantigen in mice was found to induce a cytotoxic T lymphocyte response that could lead to the onset of autoimmune diabetes, which suggests that caution should be used when applying this approach to the treatment of human autoimmune diseases.
Abstract
An antigen administered orally can induce immunological tolerance to a subsequent challenge with the same antigen. Evidence has been provided for the efficacy of this approach in the treatment of human autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. However, oral administration of autoantigen in mice was found to induce a cytotoxic T lymphocyte response that could lead to the onset of autoimmune diabetes. Thus, feeding autoantigen can cause autoimmunity, which suggests that caution should be used when applying this approach to the treatment of human autoimmune diseases.
Keywords
Immunology and MicrobiologyBiochemistry, Genetics and Molecular Biology
Manipulating the mouse embryo: A laboratory manual
4,473 Citations1986Brigid Hogan, Frank Costantini +1 more
Here are recorded the tech- niques for preparing, inserting and analysing DNA sequences, for retroviral infection of mice, for production and use of EC and EK cells as vehicles for engineered sequences and for nuclear transplantation - all against a background of the basic procedures required for pro- ducing and handling the em- bryos.
CellT cell receptor antagonist peptides induce positive selection
2,878 Citations1994Kristin A. Hogquist, Stephen C. Jameson +4 more
Results show that the process of positive selection is exquisitely peptide specific and sensitive to extremely low ligand density and support the notion that low efficacy ligands mediate positive selection.
CellAblation of “tolerance” and induction of diabetes by virus infection in viral antigen transgenic mice
1,173 Citations1991Pamela S. Ohashi, Stephan Oehen +7 more
This model indicates that self-reactive cytotoxic T cells may remain functionally unresponsive, owing to a lack of appropriate T cell activation, in so-called "T cell-mediated autoimmune diseases".
Annual Review of ImmunologyOral Tolerance: Immunologic Mechanisms and Treatment of Animal and Human Organ-Specific Autoimmune Diseases by Oral Administration of Autoantigens
900 Citations1994Howard L. Weiner, Aharon Friedman +8 more
Orally administered autoantigens suppress several experimental autoimmune models in a disease- and antigen-specific fashion; the diseases include experimental autoimmune encephalomyelitis, uveitis, and myasthenia, collagen- and adjuvant-induced arthritis, and diabetes in the NOD mouse.
NaturePeripheral deletion of antigen-reactive T cells in oral tolerance
785 Citations1995Youhai Chen, Jun-ichi Inobe +4 more
It is reported that oral antigen can delete antigen-reactive T cells in Peyer's patches, in mice transgenic for the ovalbumin-specific T-cell receptor genes, and was dependent on dosage and frequency of feeding.
ScienceEffects of Oral Administration of Type II Collagen on Rheumatoid Arthritis
631 Citations1993David E. Trentham, Roselynn Dynesius‐Trentham +6 more
Clinical efficacy of an oral tolerization approach for rheumatoid arthritis is demonstrated and a decrease in the number of swollen joints and tender joints occurred in subjects fed chicken type II collagen for 3 months but not in those that received a placebo.
ScienceDouble-Blind Pilot Trial of Oral Tolerization with Myelin Antigens in Multiple Sclerosis
587 Citations1993Howard L. Weiner, Glenn A. Mackin +5 more
Although conclusions about efficacy cannot be drawn from these data, they open an area of investigation for MS and other autoimmune diseases.
Proceedings of the National Academy of SciencesSuppression of diabetes in nonobese diabetic mice by oral administration of porcine insulin.
564 Citations1991Z J Zhang, Lance E. Davidson +2 more
It is found that oral administration of insulin delays the onset and reduces the incidence of diabetes in NOD mice over a 1-year period in animals administered 1 mg of porcine insulin orally twice a week for 5 weeks and then weekly until 1 year of age.
Immunology TodayThe regulation of immune responses to dietary protein antigens
487 Citations1987Allan McI. Mowat
Allan Mowat reviews the mechanisms underlying the induction of immunological tolerance after feeding proteins and suggests how a breakdown in oral tolerance may lead to potentially harmful hypersensitivity in the intestine.
The Journal of Experimental MedicineSystemic tolerance and secretory immunity after oral immunization.
430 Citations1980Stephen Challacombe, T. B. Tomasi
It appears that intragastric administration of soluble or particulate antigens in mice may lead to the concurrent induction of salivary antibodies and systemic suppression.
The Journal of Experimental MedicineClass I-restricted processing and presentation of exogenous cell-associated antigen in vivo.
407 Citations1990Federico Carbone, Michael J. Bevan
It is argued that class I-restricted processing and presentation of exogenous antigen can occur in vivo following immunization with cell-associated antigen.
The Journal of ImmunologySuppression of experimental autoimmune encephalomyelitis by oral administration of myelin basic protein and its fragments.
404 Citations1988Paul J. Higgins, Howard L. Weiner
Proceedings of the National Academy of SciencesSuppression of type II collagen-induced arthritis by intragastric administration of soluble type II collagen.
353 Citations1986Cathryn Nagler‐Anderson, Loretta A. Bober +3 more
Although oral administration of protein antigens may lead to specific immunologic unresponsiveness, this method of immunoregulation has not been applied to models of autoimmune disease and the overall magnitude of the antibody response is not significantly reduced in collagen-fed mice as compared to controls.
Journal of Clinical InvestigationMononuclear cell infiltration and its relation to the expression of major histocompatibility complex antigens and adhesion molecules in pancreas biopsy specimens from newly diagnosed insulin-dependent diabetes mellitus patients.
348 Citations1993Naoto Itoh, Toshiaki Hanafusa +8 more
CD8+T lymphocyte-predominant insulitis and MHC class I hyperexpression in islet cells suggests that infiltrating CD8-T lymphocytes recognize islet autoantigens in association with increased MHCclass I molecules and act as major effector cells in autoimmune response against islets cells in IDDM pancreases.
Cellular ImmunologySuppression of experimental autoimmune encephalomyelitis by the oral administration of myelin basic protein
288 Citations1988Dina M. Bitar, Caroline C. Whitacre
The oral administration of myelin basic protein to Lewis rats prior to an encephalitogenic challenge resulted in total inhibition or a significant delay in the onset of experimental autoimmune encephalomyelitis (EAE), and the specificity of MBP-induced oral tolerance was shown to be species specific.
The Journal of ImmunologyInhibition of S-antigen induced experimental autoimmune uveoretinitis by oral induction of tolerance with S-antigen.
281 Citations1990Robert B. Nussenblatt, Rachel R Caspi +5 more
It is demonstrated that Ag-specific immunomanipulation can be achieved in the EAU model by oral administration of the SAg and raise the possibility that such an approach may have practical clinical implications in uveitis as well as other human autoimmune diseases.
NatureAutoimmune diabetes as a consequence of locally produced interleukin-2
235 Citations1992William R. Heath, Janette Allison +5 more
The results indicate that autoreactive T cells that ignore self antigens may cause autoimmune diabetes when provided with exogenous 'help' in the form of interleukin-2.
PubMedGastric administration of type II collagen delays the onset and severity of collagen-induced arthritis in rats.
179 Citations1986H S Thompson, Norman A. Staines
The results indicate that materials specifically cross-reactive with autoantigens can be absorbed through the gut and can modify susceptibility to autoimmune disease.
PubMedSuppression of insulitis in non-obese diabetic (NOD) mice by oral insulin administration is associated with selective expression of interleukin-4 and -10, transforming growth factor-beta, and prostaglandin-E.
161 Citations1995Wayne W. Hancock, Malu Polanski +3 more
It is indicated that oral administration of insulin affects the development of diabetes in NOD mice through the generation of cells that elaborate immunoregulatory cytokines within the target organ and shift the balance from a Th1 to a Th2 pattern of cytokine expression.
International ImmunologyCD4<sup>+</sup> but not CD8<sup>+</sup>T cells are required for the induction of oral tolerance
151 Citations1995Paul Garside, Margaret Steel +2 more
It is shown that the induction of tolerance by feeding mice ovalbumin does not prime antigen-specific class I MHC-restricted cytotoxic T cells in vivo, and such responses are markedly suppressed in mice fed OVA, the first demonstration that specific cytot toxic responses to an exogenous antigen can be suppressed by feeding antigen.
Journal of AutoimmunityOral Administration of Human Insulin to NOD Mice Generates CD4+ T Cells that Suppress Adoptive Transfer of Diabetes
135 Citations1994Isabelle Bergerot, Nicole Fabien +2 more
It is demonstrated that feeding 6-week-old female mice with 20 units of human insulin every 2-3 days for 30 days induces an active mechanism of suppression through the generation of regulatory T cells that is associated with protection from clinical diabetes.
Journal of Allergy and Clinical ImmunologyInhibition of homocytotropic antibody responses in adult inbred mice by previous feeding of the specific antigen
104 Citations1977Nelson M. Vaz, Luiz C.S. Maia +2 more
Profound and prolonged states of specific immunologic tolerance were induced in adult mice of high-responder genetic background by a single exposure to moderate doses of the specific antigen by digestive route.
The Journal of ImmunologyOral administration of an immunodominant human collagen peptide modulates collagen-induced arthritis
102 Citations1995Sanjay D. Khare, Christopher J. Krco +3 more
Suppression of CIA at the effector phase by oral administration of HuCII peptide suggests a potential immunotherapeutic use of collagen II peptide in the treatment of human RA.
The Journal of ImmunologyOral antigen inhibits priming of CD8+ CTL, CD4+ T cells, and antibody responses while activating CD8+ suppressor T cells
99 Citations1996Yong Ke, Judith A. Kapp
The data show that multiple, intragastric doses of native OVA inhibited priming of CD8+ CTL precursors and also inhibited CD4+ T cells and Ab responses and the observed tolerance is specific to the orally administered Ag.
Immunology TodayCould specific oral tolerance be a therapy for autoimmune disease?
95 Citations1990H Caldwell Stephen, Grace Thompson +1 more
The nature and mechanisms of this form of tolerance are reviewed and its possible applications in the control of human autoimmune diseases are discussed.
International Archives of Allergy and Applied ImmunologyOrally Induced Tolerance
88 Citations2009Richard G. Titus, Jacques M. Chiller
It was shown that whereas intragastric exposure of mice to the T-dependent antigens oval-bumin, bovine serum albumin, and OVO are known to cause oral tolerance, oral tolerance in mice exposed to OVOs is not affected.
PubMedPriming of systemic and local delayed-type hypersensitivity responses by feeding low doses of ovalbumin to mice.
62 Citations1989Alan Lamont, Allan McI. Mowat +1 more
It is concluded that feeding certain low doses of protein antigens can induce priming of local and systemic DTH responses rather than the immune tolerance which is normally found, which may be highly dependent on the dose of dietary antigen at the time of first encounter.
The Journal of ImmunologyAutoimmunity caused by ignorant CD8+ T cells is transient and depends on avidity
57 Citations1995William R. Heath, Freda Karamalis +2 more
It is indicated that the duration of priming stimulus and the avidity of the autoreactive CD8+ cells profoundly influence the severity of autoimmune disease.
DiabetesAberrant Activation of CD8+ T-cell and CD8+ T-Cell Subsets in Patients With Newly Diagnosed IDDM
27 Citations1995B Hehmke, Dietrich Michaelis +3 more
An important role for CD8+ T-lymphocytes in IDDM is suggested and the possibility that these lymphocytes might be the relevant target for early immunotherapy in patients with recent disease onset is raised.
European Journal of ImmunologyExpression of a gastric autoantigen in pancreatic islets results in non‐destructive insulitis after neonatal thymectomy
20 Citations1995Simon P. Barrett, Ian R. van Driel +4 more
Insulitis in the RIP‐H/Kβ mice appears to be dependent on a T cell response to the H/K ATPase β subunit, the first example where an organ‐specific initiating autoantigen has been expressed in another peripheral tissue.
NatureDevernalization of Spring Rye by Anærobic Conditions and Revernalisation by Low Temperature
10 Citations1937F. G. Gregory, O. N. Purvis
Molecular MedicineAntigen-Specific Therapy for Autoimmune Disease: Prospects for the Prevention of Insulin-Dependent Diabetes
7 Citations1995Leonard C. Harrison
A range of strategies have been shown to prevent the induc-tion or favorably modify the natural history ofautoimmunedisease inrodents, and strategies cen-tered on autoantigens have a clear advantage in humanautoimmune disease.