title: Apoptosis as a mechanism of T-regulatory cell homeostasis and suppression.
abstract: Activation-induced cell death is a general mechanism of immune homeostasis through negative regulation of clonal expansion of activated immune cells. This mechanism is involved in the maintenance of self- and transplant tolerance through polarization of the immune responses. The Fas/Fas-ligand interaction is a major common executioner of apoptosis in lymphocytes, with a dual role in regulatory T cell (Treg) function: Treg cell homeostasis and Treg cell-mediated suppression. Sensitivity to apoptosis and the patterns of Treg-cell death are of outmost importance in immune homeostasis that affects the equilibrium between cytolytic and suppressor forces in activation and termination of immune activity. Naive innate (naturally occurring) Treg cells present variable sensitivities to apoptosis, related to their turnover rates in tissue under steady state conditions. Following activation, Treg cells are less sensitive to apoptosis than cytotoxic effector subsets. Their susceptibility to apoptosis is influenced by cytokines within the inflammatory environment (primarily interleukin-2), the mode of antigenic stimulation and the proliferation rates. Here, we attempt to resolve some controversies surrounding the sensitivity of Treg cells to apoptosis under various experimental conditions, to delineate the function of cell death in regulation of immunity.
authors.affiliation: Department of Microbiology and Immunology, Institute for Cellular Therapeutics, University of Louisville, Louisville, KY, USA.
authors.forename: Esma S
authors.initials: ES
authors.lastname: Yolcu
authors.forename: Shifra
authors.initials: S
authors.lastname: Ash
authors.forename: Ayelet
authors.initials: A
authors.lastname: Kaminitz
authors.forename: Yuval
authors.initials: Y
authors.lastname: Sagiv
authors.forename: Nadir
authors.initials: N
authors.lastname: Askenasy
authors.forename: Shai
authors.initials: S
authors.lastname: Yarkoni
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D003520:Cyclophosphamide / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D053222:Fas Ligand Protein / Q000378:metabolism; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D014740:Vidarabine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine