Summary
Abnormal expression of key signaling molecules and defective functions of T lymphocytes play a significant role in the pathogenesis of systemic lupus erythematosus (SLE). T-cell receptor (TCR)/CD3-mediated stimulation of SLE T cells shows increased protein tyrosine phosphorylation of cellular proteins, with faster kinetics, heightened calcium response, and decreased interleukin (IL)-2 production. The molecular mechanism of T-cell signaling abnormalities in SLE T cells is complex and cannot be explained fully by the current theories of T-cell signaling. Current research on lymphocyte signaling abnormalities in SLE has been directed toward investigating various factors that contribute to abnormal tyrosine phosphorylation, intracellular calcium response, and cytokine production. Latest developments suggest multiple components, including altered receptor structure, supramolecular assembly, modulation of membrane clustering, aberrant cellular distribution, and precompartmentalization with lipid rafts invariably contributing to abnormal T-cell signaling in SLE T cells. The methods and protocols described here pertaining to T-cell signaling abnormalities in SLE T cells are very much optimized in many ways, and they were derived by the combined tasks and continuous efforts of many researchers in the laboratory over a long period. These simplified protocols can be readily applied to study T-cell signaling abnormalities in SLE to identify the genetic, molecular, and biochemical factors contributing to aberrant immune cell function and unravel the pathophysiology of SLE.
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References
Irving, B. A., Chan, A. C., and Weiss, A. (1993) Functional characterization of a signal transducing motif present in the T cell antigen receptor zeta chain. J. Exp. Med. 177, 1093ā1103.
Zenner, G., Vorherr, T., Mustelin, T., and Burn, P. (1996) Differential and multtiple binding of signal transducing molecules to the ITAMs of the TCR-zeta chain. J. Cell Biochem. 63, 94ā103.
Kersh, E. N., Shaw, A. S., and Allen, P. M. (1998) Fidelity of T celll activation through multistep T cell receptor zeta phosphorylation. Science 281, 572ā575.
Kersh, E. N., Kersh, G. J., and Allen, P. M. (1999) Partially phosphorylated T cell receptor zeta molecules can inhibit T cell activation. J. Exp. Med. 190, 1627ā1636.
Weiss, A. and Littman, D. R. (1994) Signal transduction by lymphocyte antigen receptors. Cell 76, 263ā274.
Wange, R. L. and Samelson, L. E. (1996) Complex complexes: signaling at the TCR. Immunity 5, 197ā205.
Falkoff, R. M., Peters, M., and Fauci, A. S. (1982) T cell enrichment and depletion of human peripheral blood mononuclear cell preparations. Unexpected findings in the study of the functional activities of the separated populations. J. Immunol. Meth. 50, 39ā49.
Liossis, S. N., Ding, D. Z., Dennis, G. J., and Tsokos, G. C. (1998) Altered pattern of TCR/CD3-mediated protein-tyrosyl phosphorylattion in T cells from patients with systemic lupus erythematosus. Deficient expression of the T-cell receptor zeta chain. J. Clin. Invest. 101, 1448ā1457.
Laemmli, U. K. (1970) Cleavage of structural prooteins during the assembly of the head of bacteriophage T4. Nature 227, 680ā685.
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Ā© 2004 Humana Press Inc., Totowa, NJ
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Nambiar, M.P., Krishnan, S., Tsokos, G.C. (2004). T-Cell Signaling Abnormalities in Human Systemic Lupus Erythematosus. In: Perl, A. (eds) Autoimmunity. Methods in Molecular Medicineā¢, vol 102. Humana Press. https://doi.org/10.1385/1-59259-805-6:031
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DOI: https://doi.org/10.1385/1-59259-805-6:031
Publisher Name: Humana Press
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Online ISBN: 978-1-59259-805-2
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