Mature T lymphocyte apoptosis - Immune regulation in a dynamic and unpredictable antigenic environment

Michael Lenardo, Francis Ka Ming Chan, Felicita Hornung, Hugh McFarland, Richard Siegel, Jin Wang, Lixin Zheng

    Research output: Contribution to journalReview articlepeer-review

    861 Scopus citations

    Abstract

    Apoptosis of mature T lymphocytes preserves peripheral homeostasis and tolerance by countering the profound changes in the number and types of T cells stimulated by diverse antigens. T cell apoptosis occurs in at least two major forms: antigen-driven and lymphokine withdrawal. These forms of death are controlled in response to local levels of IL-2 and antigen in a feedback mechanism termed propriocidal regulation. Active antigen-driven death is mediated by the expression of death cytokines such as FasL and TNF. These death cytokines engage specific receptors that assemble caspase-activating protein complexes. These signaling complexes tightly regulate cell death but are vulnerable to inherited defects. Passive lymphokine withdrawal death may result from the cytoplasmic activation of caspases that is regulated by mitochondria and the Bcl-2 protein. The human disease, Autoimmune Lymphoproliferative Syndrome (ALPS) is due to dominant-interfering mutations in the Fas/APO-1/CD95 receptor and other components of the death pathway. The study of ALPS patients reveals the necessity of apoptosis for preventing autoimmunity and allows the genetic investigation of apoptosis in humans. Immunological, cellular, and molecular evidence indicates that throughout the life of a T cell, apoptosis may be evoked in excessive, harmful, or useless clonotypes to preserve a healthy and balanced immune system.

    Original languageEnglish (US)
    Pages (from-to)221-253
    Number of pages33
    JournalAnnual Review of Immunology
    Volume17
    DOIs
    StatePublished - 1999

    Keywords

    • Autoimmune Lymphoproliferative Syndrome
    • Bcl- 2
    • Caspase
    • Cytokine
    • Death
    • Fas/APO-1/CD95
    • Feedback
    • Lymphokine
    • Propriocidal
    • Receptor
    • Tumor necrosis factor

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

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