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Related Experiment Videos

Genetically restricted antigen presentation for immunological tolerance and suppression.

A Lowy, J A Drebin, J G Monroe

    Nature
    |March 22, 1984
    PubMed
    Summary

    Immune responses depend on antigen presentation. T helper cell activation requires I-A positive cells, while T suppressor cells need I-J positive cells for optimal T-cell regulation.

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    Area of Science:

    • Immunology
    • T cell biology
    • Immune regulation

    Background:

    • T cell activation typically requires antigen recognition alongside self Ia determinants.
    • The necessity of this for inducing unresponsiveness and active suppression of T cells remains unclear.
    • The regulation of delayed-type hypersensitivity (DTH) responses in mice is a key area of study.

    Purpose of the Study:

    • To investigate the distinct requirements for T cell activation, suppression, and tolerance induction.
    • To elucidate the role of antigen-presenting cells (APCs) with specific Ia determinants in these processes.
    • To understand the mechanisms regulating hapten-specific T cell responses.

    Main Methods:

    • Studied the delayed-type hypersensitivity (DTH) response in mice.

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  • Administered haptenated syngeneic cells via subcutaneous (s.c.) and intravenous (i.v.) routes.
  • Investigated the role of I-A and I-J positive antigen-presenting cells (APCs) in T cell activation and suppression.

    • Main Results:

    • Subcutaneous injection activated T helper cells, while intravenous injection induced unresponsiveness and T suppressor cells.
    • T helper cell activation critically depends on antigen presentation by I-A-positive APCs.
    • First-order T suppressor cell activation requires antigen presentation on I-J-positive APCs, but tolerance can occur independently of I-J presentation.

    Conclusions:

    • Distinct antigen presentation pathways and administration routes dictate immune outcomes: immunity, suppression, or non-transferable tolerance.
    • Non-transferable T-cell tolerance is I-A-dependent, genetically restricted, and can be induced without I-J presentation.
    • These findings highlight the complexity of T cell regulation and the critical role of APCs in directing immune responses.