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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 Jan 4;91(1):38–42. doi: 10.1073/pnas.91.1.38

Anergic T-lymphocyte clones have altered inositol phosphate, calcium, and tyrosine kinase signaling pathways.

T F Gajewski 1, D Qian 1, P Fields 1, F W Fitch 1
PMCID: PMC42881  PMID: 7506419

Abstract

Full activation of TH1 helper T lymphocytes requires ligation of the specific T-cell antigen receptor (TCR) and a second signal provided by costimulator molecule(s) expressed on particular antigen-presenting cells. Stimulation via the TCR complex alone generates a subsequent unresponsive state characterized by an inability to produce interleukin 2. We report here that such anergic cells exhibit multiple alterations in TCR-associated signaling. The basal levels of intracellular free calcium and phosphatidylinositol 1,4,5-trisphosphate are elevated in anergic cells, and the levels fail to increase significantly upon subsequent restimulation. Examination of phospholipase C-gamma 1 reveals evidence for post-translational modification, correlating with increased tyrosine phosphorylation of the molecule. Tyrosine phosphorylation of additional substrates identified from whole-cell lysates also is altered compared to untreated cells, suggesting a modification in net tyrosine kinase activity. Although the level of kinase activity present in TCR/CD3 or Lck immunoprecipitates is modestly altered after induction of anergy, there is a dramatic increase in specific Fyn-associated tyrosine kinase activity in anergic cells and increased phosphorylation of a 110-kDa protein that is coimmunoprecipitated with Fyn. These results are consistent with a model in which anergic TH1 lymphocytes display a fundamental alteration in TCR-mediated tyrosine kinase activity, associated with changes in phospholipase C-gamma 1, inositol phosphates, and intracellular free calcium.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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