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Related Experiment Videos

Aberrant tolerance induction with cationic antigens

M J Jacobs1, A E van den Hoek, L B van de Putte

  • 1Department of Rheumatology, University Hospital Nijmegen, The Netherlands.

Scandinavian Journal of Immunology
|January 1, 1993
PubMed
Summary
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Oral administration of native proteins effectively induces tolerance and suppresses cell-mediated immunity (CMI). Cationic protein derivatives, however, showed limited capacity to suppress CMI, suggesting antigen structure is crucial for immunointervention strategies.

Area of Science:

  • Immunology
  • Allergy and immunology

Background:

  • Oral and intravenous administration of antigens can induce immune tolerance.
  • Cell-mediated immunity (CMI) plays a role in various immune responses and diseases.
  • Understanding antigen-specific tolerance is key for developing immunointervention strategies.

Purpose of the Study:

  • To compare the capacity of native proteins and their cationic derivatives to induce tolerance and suppress CMI.
  • To investigate the effectiveness of different administration routes (oral and i.v.) in inducing tolerance.
  • To explore the potential of antigen modification for modulating immune responses, particularly in the context of arthritis.

Main Methods:

  • Induction of tolerance in female C57B1/6 mice via oral or intravenous administration of protein antigens (chicken egg albumin - OVA, bovine serum albumin - BSA) and their cationic derivatives (amidated - aOVA, aBSA; methylated - mBSA).

Related Experiment Videos

  • Measurement of cell-mediated immunity (CMI) suppression using a delayed type hypersensitivity (DTH) test.
  • Cross-experiments involving pre-immunized mice to assess tolerance induction and specificity.
  • Testing of cationic derivatives in a chronic arthritis model.

    • Main Results:

    • Oral administration of native proteins (0.5 mg) significantly suppressed CMI.
    • Cationic derivatives (aOVA, aBSA, mBSA) failed to suppress CMI at doses ranging from 50 micrograms to 50 mg.
    • Intravenous administration of native OVA (25 micrograms) induced clear suppression, while higher doses of aOVA (500 micrograms) showed only marginal suppression.
    • Significant suppression was achieved with aOVA (up to 2.5 mg) in a chronic arthritis model.
    • Tolerance induction was antigen-specific, with limited cross-reactivity observed.

    Conclusions:

    • The structure of the antigen is critical for inducing immune tolerance and suppressing CMI.
    • Native proteins are more potent inducers of tolerance than their cationic derivatives.
    • Immunointervention strategies, particularly for conditions like human arthritis, may depend heavily on the specific antigen used.
    • Further research into antigen modification could offer new therapeutic avenues for immune modulation.