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

Published

Journal Article (Review)

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.

Full Text

Duke Authors

Cited Authors

  • Lenardo, M; Chan, KM; Hornung, F; McFarland, H; Siegel, R; Wang, J; Zheng, L

Published Date

  • January 1999

Published In

Volume / Issue

  • 17 /

Start / End Page

  • 221 - 253

PubMed ID

  • 10358758

Pubmed Central ID

  • 10358758

Electronic International Standard Serial Number (EISSN)

  • 1545-3278

International Standard Serial Number (ISSN)

  • 0732-0582

Digital Object Identifier (DOI)

  • 10.1146/annurev.immunol.17.1.221

Language

  • eng