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T cell anergy

J M LaSalle¹, D A Hafler

¹Laboratory of Molecular Immunology, Brigham and Women's Hospital, Boston, Massachusetts 02115.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology

|June 1, 1994

Summary

T cell anergy, a state of functional inactivation, is crucial for immunologic self-tolerance. Human T cells presenting antigen can induce this anergy, acting as a fail-safe mechanism against autoreactivity.

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Area of Science:

Immunology
Cellular Biology

Background:

T cell clonal anergy is a proposed mechanism for immunologic self-tolerance.
The role of antigen-presenting cells in T cell activation versus anergy is under investigation.
Human T cells express MHC class II molecules upon activation, enabling antigen presentation.

Purpose of the Study:

To investigate the role of human T cells in inducing T cell clonal anergy.
To understand how T cell-mediated antigen presentation influences T cell responsiveness.
To explore T cell anergy as a potential fail-safe mechanism in self-tolerance.

Main Methods:

Studying T cell activation and functional inactivation.
Analyzing MHC class II-restricted antigen presentation by human T cells.
Investigating T cell responses to high-dose antigen stimulation after T cell presentation.

Main Results:

Human T cells, after activation, can present high concentrations of degraded peptide antigen to autologous T cells, inducing clonal anergy.
Unlike low-dose anergy, T cell-induced anergy involves initial proliferation followed by secondary unresponsiveness.
This process occurs even with high-dose antigenic stimulation.

Conclusions:

T cell presentation of antigen is a novel mechanism contributing to immunologic self-tolerance.
This mechanism acts as a fail-safe, anergizing expanded autoreactive T cells in high self-antigen environments.
T cell-mediated anergy provides robust self-tolerance by inducing both proliferation and subsequent unresponsiveness.

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