Autocrine feedback death and the regulation of mature T lymphocyte antigen responses.
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.
Lenardo
M J
MJ
Laboratory of Immunology, National Institute for Allergy and Infectious Diseases, Bethesda, MD 20892-1982, USA.
Boehme
S
S
Chen
L
L
Combadiere
B
B
Fisher
G
G
Freedman
M
M
McFarland
H
H
Pelfrey
C
C
Zheng
L
L
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
D000941:Antigens; D006133:Growth Substances