title: Balancing the immune system for tolerance: a case for regulatory CD4 cells.
abstract: In the past, tolerance mechanisms have focused on processes that involve elimination (deletion) or paralysis (anergy) of immune responses. It is now becoming clearer that peripheral tolerance to antigen depends on the generation of regulatory cells that function to maintain the tolerant state. The development of peripheral tolerance may require that the immune system utilize several strategies, including deletion, anergy, and immunoregulatory pathways, and these strategies may overlap. Recent investigations using animal models of transplantation tolerance have demonstrated that immunoregulatory CD4 mechanisms may play a central role in limiting organ-destructive immune responses. In this Overview, we discuss the rationale behind the need for invoking active regulatory mechanisms in peripheral immunologic tolerance and summarize the data that support or refute a CD4 regulatory mechanism.
authors.affiliation: Department of Veterans Affairs Medical Center and Department of Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
authors.forename: E H
authors.initials: EH
authors.lastname: Field
authors.forename: Q
authors.initials: Q
authors.lastname: Gao
authors.forename: N X
authors.initials: NX
authors.lastname: Chen
authors.forename: T M
authors.initials: TM
authors.lastname: Rouse
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D017635:Clonal Anergy / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology; D007376:Interleukin-2 / Q000502:physiology
chemical_list: D007376:Interleukin-2