title: Autocrine feedback death and the regulation of mature T lymphocyte antigen responses.
abstract: Antigen-induced T cell death is an important regulatory mechanism in the peripheral immune system. Evidence suggests that this process depends on T cell growth-inducing lymphokines such as IL-2 and occurs in proportion to the degree of T cell receptor occupancy. Strong T cell receptor stimulation leads to the synthesis of death molecules such as Fas ligand and tumor necrosis factor that cause T cell suicide. We propose that T cell death under these circumstances is the culmination of a feedback control mechanism termed propriocidal regulation or autocrine feedback death that regulates the expansion of specific T cell clones under conditions of high lymphokine and antigen load. In a quasi-stochastic system such as the antigen receptor repertoire, feedback information may be essential for the appropriate regulation of peripheral immune responses. Our understanding of this feedback mechanism affords a means to manipulate antigen-specific T cell death in vivo. The application of this approach to the therapy of T cell-medicated immunological diseases is discussed.
authors.affiliation: Laboratory of Immunology, National Institute for Allergy and Infectious Diseases, Bethesda, MD 20892-1982, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Lenardo
authors.forename: S
authors.initials: S
authors.lastname: Boehme
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.forename: B
authors.initials: B
authors.lastname: Combadiere
authors.forename: G
authors.initials: G
authors.lastname: Fisher
authors.forename: M
authors.initials: M
authors.lastname: Freedman
authors.forename: H
authors.initials: H
authors.lastname: McFarland
authors.forename: C
authors.initials: C
authors.lastname: Pelfrey
authors.forename: L
authors.initials: L
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D005246:Feedback; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
chemical_list: D000941:Antigens; D006133:Growth Substances