Annu Rev Immunol. 2003;21:305-34. Epub 2001 Dec 19.
T cell anergy.
Schwartz RH1.
Laboratory of Cellular and Molecular Immunology, National Institutes of Health, Bethesda, Maryland 20892-0420, USA. rs34r@nih.gov
T cell anergy is a tolerance mechanism in which the lymphocyte is intrinsically functionally inactivated following an antigen encounter, but remains alive for an extended period of time in a hyporesponsive state. Models of T cell anergy affecting both CD4(+) and CD8(+) cells fall into two broad categories. One, clonal anergy, is principally a growth arrest state, whereas the other, adaptive tolerance or in vivo anergy, represents a more generalized inhibition of proliferation and effector functions. The former arises from incomplete T cell activation, is mostly observed in previously activated T cells, is maintained by a block in the Ras/MAP kinase pathway, can be reversed by IL-2 or anti-OX40 signaling, and usually does not result in the inhibition of effector functions. The latter is most often initiated in naïve T cells in vivo by stimulation in an environment deficient in costimulation or high in coinhibition. Adaptive tolerance can be induced in the thymus or in the periphery. The cells proliferate and differentiate to varying degrees and then downregulate both functions in the face of persistent antigen. The state involves an early block in tyrosine kinase activation, which predominantly inhibits calcium mobilization, and an independent mechanism that blocks signaling through the IL-2 receptor. Adaptive tolerance reverses in the absence of antigen. Aspects of both of the anergic states are found in regulatory T cells, possibly preventing them from dominating initial immune responses to foreign antigens and shutting down such responses prematurely.
10.1146/annurev.immunol.21.120601.141110
Adaptation, Physiological
Adoptive Transfer
Antigen Presentation
Antigens, CD
Antigens, Differentiation/metabolism
CD4-Positive T-Lymphocytes/cytology
CD4-Positive T-Lymphocytes/immunology
CTLA-4 Antigen
Clonal Anergy*
Immunoconjugates*
Intercellular Adhesion Molecule-1/metabolism
Models, Immunological
T-Lymphocytes/cytology*
T-Lymphocytes/immunology*
T-Lymphocytes/metabolism
Antigens, Differentiation
CTLA4 protein, human
Ctla4 protein, mouse
Immunoconjugates
Intercellular Adhesion Molecule-1