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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review

Clonal Anergy

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Disease relevance of Clonal Anergy

  • Nevertheless, this induction of clonal anergy did not interfere with the capacity of naive T cells to differentiate into Th1-like effector cells, nor did it prevent such helper cells from participating in T-dependent IgG2a anti-hapten responses and delayed-type hypersensitivity reactions [1].
  • In this regard, we recently reported that a human melanoma cell line (sMC) expressing MHC class II, was able to induce clonal anergy in a specific, MHC-restricted CD-4+ T cell clone (sTC3) [2].

High impact information on Clonal Anergy


Biological context of Clonal Anergy


Anatomical context of Clonal Anergy

  • Exposure of mature CD4+ T cells in the peripheral immune system to peptide-antigen/MHC complexes in the absence of a threat of infection induces tolerance to the antigen as a result of both a decreased clonal frequency (peripheral deletion) and the induction of proliferative unresponsiveness (clonal anergy) in the survivors [12].
  • These findings suggest participation of both clonal anergy, and active suppressor cells in the liposome-mediated suppression of CR-EAE in the Lewis rat [13].
  • Yet, neoplastic astroglia appear to acquire the capacity to downregulate microglial MHC class II expression and, at the same time, may induce T-cell clonal anergy through aberrant expression of MHC class II molecules [14].

Associations of Clonal Anergy with chemical compounds

  • CONCLUSIONS: Because donor-specific tolerance persisted long after cessation of peptide administration and did not occur when cyclosporin A was omitted from the immunosuppressive regimen, the mechanism may involve induction of clonal anergy [15].

Gene context of Clonal Anergy

  • CD2 is involved in maintenance and reversal of human alloantigen-specific clonal anergy [16].
  • This state was contrasted with T cell clonal anergy in which the RAS/MAPK pathway was preferentially impaired and there was much less inhibition of Zap70 kinase activity [17].
  • Oral tolerance is mediated through active suppression by Th2 or TGF-beta-secreting cells or clonal anergy/deletion, depending on the Ag dose used, with low dose favoring active suppression and high dose favoring anergy/deletion [18].
  • These events were strongly suggestive of a clonal anergy affecting more profoundly Th2 than the Th1 subsets [19].
  • Costimulation (signal 2) has been proposed to inhibit the induction of T cell clonal anergy by either directly antagonizing negative signals arising from TCR engagement (signal 1) or by synergizing with signal 1 to produce IL-2, which in turn leads to proliferation and dilution of negative regulatory factors [20].


  1. Peripheral immune tolerance blocks clonal expansion but fails to prevent the differentiation of Th1 cells. Malvey, E.N., Jenkins, M.K., Mueller, D.L. J. Immunol. (1998) [Pubmed]
  2. Prevention of anergy induction in cloned T cells by interleukin 12. Becker, J.C., Bröcker, E.B. Exp. Dermatol. (1994) [Pubmed]
  3. Requirement for T-cell apoptosis in the induction of peripheral transplantation tolerance. Wells, A.D., Li, X.C., Li, Y., Walsh, M.C., Zheng, X.X., Wu, Z., Nuñez, G., Tang, A., Sayegh, M., Hancock, W.W., Strom, T.B., Turka, L.A. Nat. Med. (1999) [Pubmed]
  4. CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Harding, F.A., McArthur, J.G., Gross, J.A., Raulet, D.H., Allison, J.P. Nature (1992) [Pubmed]
  5. Blocked signal transduction to the ERK and JNK protein kinases in anergic CD4+ T cells. Li, W., Whaley, C.D., Mondino, A., Mueller, D.L. Science (1996) [Pubmed]
  6. Transactivation by AP-1 is a molecular target of T cell clonal anergy. Kang, S.M., Beverly, B., Tran, A.C., Brorson, K., Schwartz, R.H., Lenardo, M.J. Science (1992) [Pubmed]
  7. Signaling through CD28 and CTLA-4 controls two distinct forms of T cell anergy. Wells, A.D., Walsh, M.C., Bluestone, J.A., Turka, L.A. J. Clin. Invest. (2001) [Pubmed]
  8. Antagonistic roles for CTLA-4 and the mammalian target of rapamycin in the regulation of clonal anergy: enhanced cell cycle progression promotes recall antigen responsiveness. Vanasek, T.L., Khoruts, A., Zell, T., Mueller, D.L. J. Immunol. (2001) [Pubmed]
  9. Clonal anergy is maintained independently of T cell proliferation. Colombetti, S., Benigni, F., Basso, V., Mondino, A. J. Immunol. (2002) [Pubmed]
  10. Early growth response gene-2, a zinc-finger transcription factor, is required for full induction of clonal anergy in CD4+ T cells. Harris, J.E., Bishop, K.D., Phillips, N.E., Mordes, J.P., Greiner, D.L., Rossini, A.A., Czech, M.P. J. Immunol. (2004) [Pubmed]
  11. Evidence for repression of IL-2 gene activation in anergic T cells. Telander, D.G., Malvey, E.N., Mueller, D.L. J. Immunol. (1999) [Pubmed]
  12. The role of clonal anergy in the avoidance of autoimmunity: inactivation of autocrine growth without loss of effector function. Malvey, E.N., Telander, D.G., Vanasek, T.L., Mueller, D.L. Immunol. Rev. (1998) [Pubmed]
  13. Treatment of spinal cord-induced experimental allergic encephalomyelitis in the Lewis rat with liposomes presenting central nervous system antigens. Stein, C.S., St Louis, J., Gilbert, J.J., Strejan, G.H. J. Neuroimmunol. (1990) [Pubmed]
  14. Differential expression of MHC class II molecules by microglia and neoplastic astroglia: relevance for the escape of astrocytoma cells from immune surveillance. Tran, C.T., Wolz, P., Egensperger, R., Kösel, S., Imai, Y., Bise, K., Kohsaka, S., Mehraein, P., Graeber, M.B. Neuropathol. Appl. Neurobiol. (1998) [Pubmed]
  15. Induction of tolerance in rodent cardiac allotransplantation using an MHC class I-derived peptide and cyclosporin A. Masroor, S., Itescu, S., Artrip, J.H., Minanov, O.P., Buelow, R., Michler, R.E. Ann. Thorac. Surg. (1998) [Pubmed]
  16. CD2 is involved in maintenance and reversal of human alloantigen-specific clonal anergy. Boussiotis, V.A., Freeman, G.J., Griffin, J.D., Gray, G.S., Gribben, J.G., Nadler, L.M. J. Exp. Med. (1994) [Pubmed]
  17. Adaptive tolerance and clonal anergy are distinct biochemical states. Chiodetti, L., Choi, S., Barber, D.L., Schwartz, R.H. J. Immunol. (2006) [Pubmed]
  18. B7.2 (CD86) but not B7.1 (CD80) costimulation is required for the induction of low dose oral tolerance. Liu, L., Kuchroo, V.K., Weiner, H.L. J. Immunol. (1999) [Pubmed]
  19. Inducing tolerance by intranasal administration of long peptides in naive and primed CBA/J mice. Astori, M., von Garnier, C., Kettner, A., Dufour, N., Corradin, G., Spertini, F. J. Immunol. (2000) [Pubmed]
  20. Inhibition of cell cycle progression by rapamycin induces T cell clonal anergy even in the presence of costimulation. Powell, J.D., Lerner, C.G., Schwartz, R.H. J. Immunol. (1999) [Pubmed]
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