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Adjuvant effect on maintenance and escape from tolerence.

M M Azar, G Lucena

    Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)
    |September 1, 1975
    PubMed
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    Inducing immune tolerance in mice with deaggregated human gamma globulin (HGG) is robust. However, early administration of adjuvant with HGG can prevent tolerance, especially with certain mouse strains and adjuvant compositions.

    Area of Science:

    • Immunology
    • Tolerance Induction
    • Adjuvant Effects

    Background:

    • Immune tolerance is crucial for preventing autoimmune responses.
    • Deaggregated human gamma globulin (HGG) is used to induce tolerance in experimental models.
    • Adjuvants can modulate immune responses, but their effect on tolerance induction is complex.

    Purpose of the Study:

    • To investigate the stability of HGG-induced immune tolerance in mice.
    • To determine if early administration of adjuvant impacts tolerance induction.
    • To explore factors influencing the circumvention of established tolerance.

    Main Methods:

    • Induction of tolerance in mice using deaggregated HGG.
    • Subsequent challenges with HGG in saline or adjuvant.

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  • Administration of radiolabeled HGG to assess tolerance persistence.
  • Early co-administration of HGG with varying amounts of mycobacterial adjuvant.

    • Main Results:

    • HGG-induced tolerance is generally persistent and resistant to immune elimination doses.
    • Early administration (5 days post-tolerance induction) of adjuvant with HGG prevents tolerance.
    • Earlier challenge (5 vs. 7 days) after tolerance induction leads to increased tolerance circumvention.
    • Tolerance circumvention is influenced by adjuvant mycobacterial content and murine strain.

    Conclusions:

    • Immune tolerance induced by HGG is robust but can be abrogated by early adjuvant intervention.
    • The timing of adjuvant administration relative to antigen exposure is critical for tolerance induction.
    • Adjuvant composition and host genetics play significant roles in modulating immune tolerance.