T cell anergy and costimulation.
T lymphocytes play a key role in immunity by distinguishing self from nonself peptide antigens and regulating both the cellular and humoral arms of the immune system. Acquired, antigen-specific unresponsiveness is an important mechanism by which T cell responses to antigen are regulated in vivo. Clonal anergy is the term that describes T cell unresponsiveness at the cellular level. Anergic T cells do not proliferate or secrete interleukin (IL)-2 in response to appropriate antigenic stimulation. However, anergic T cells express the IL-2 receptor, and anergy can be broken by exogenous IL-2. Anergy can be induced by submitogenic exposure to peptide antigen in the absence of a costimulatory signal provided by soluble cytokines or by interactions between costimulatory receptors on T cells and counter-receptors on antigen-presenting cells. The molecular events that mediate the induction and maintenance of T cell anergy are the focus of this review. The molecular consequences of CD28-B7 interaction are discussed as a model for the costimulatory signal that leads to T cell activation rather than the induction of anergy.
Appleman
Leonard J
LJ
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Boussiotis
Vassiliki A
VA
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism; D018106:CD28 Antigens / Q000737:chemistry / Q000378:metabolism; D060908:CTLA-4 Antigen; D002448:Cell Adhesion; D017635:Clonal Anergy; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D011948:Receptors, Antigen, T-Cell; D019869:Phosphatidylinositol 3-Kinases; D020558:GTP Phosphohydrolases