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

• Deletion has been implicated in central tolerance, whereas peripheral tolerance has generally been ascribed to clonal anergy and/or active immunoregulatory states [3].
• Exposure of T-cell clones to complexes of antigen with major histocompatibility complex molecules in the absence of the co-stimulatory signal induces a state of clonal anergy [4].
• T cells activated by antigen receptor stimulation in the absence of accessory cell-derived costimulatory signals lose the capacity to synthesize the growth factor interleukin-2 (IL-2), a state called clonal anergy [5].
• These results suggest that a specific block in the activation of ERK and JNK contributes to defective IL-2 production in clonal anergy [5].
• Transactivation by AP-1 is a molecular target of T cell clonal anergy [6].

Biological context of Clonal Anergy

• Also, cell division per se is not sufficient for anergy avoidance: the few T cells that undergo multiple rounds of cell division during overt CD28 costimulatory blockade do not escape the ultimate induction of clonal anergy [7].
• 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 [8].
• Our data instead indicate that reversal of clonal anergy specifically requires an IL-2-dependent, rapamycin-sensitive signal, which is delivered independently of cell proliferation [9].
• Early growth response gene-2, a zinc-finger transcription factor, is required for full induction of clonal anergy in CD4+ T cells [10].
• The induction of clonal anergy in a T cell inhibits IL-2 secretion because of the development of a proximal signal transduction defect [11].

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].

References