Decreased SAP Expression in T Cells from Patients with Systemic Lupus Erythematosus Contributes to Early Signaling Abnormalities and Reduced IL-2 Production

T cells from patients with systemic lupus erythematosus (SLE) display a number of abnormalities, including increased early signaling events following engagement of the TCR. Signaling lymphocytic activation molecule family cell surface receptors and the X-chromosome–defined signaling lymphocytic acti...

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Published inThe Journal of immunology (1950) Vol. 196; no. 12; pp. 4915 - 4924
Main Authors Karampetsou, Maria P, Comte, Denis, Kis-Toth, Katalin, Terhorst, Cox, Kyttaris, Vasileios C, Tsokos, George C
Format Journal Article
LanguageEnglish
Published United States 15.06.2016
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ISSN0022-1767
1550-6606
1550-6606
DOI10.4049/jimmunol.1501523

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Summary:T cells from patients with systemic lupus erythematosus (SLE) display a number of abnormalities, including increased early signaling events following engagement of the TCR. Signaling lymphocytic activation molecule family cell surface receptors and the X-chromosome–defined signaling lymphocytic activation molecule-associated protein (SAP) adaptor are important in the development of several immunocyte lineages and modulating the immune response. We present evidence that SAP protein levels are decreased in T cells and in their main subsets isolated from 32 women and three men with SLE, independent of disease activity. In SLE T cells, SAP protein is also subject to increased degradation by caspase-3. Forced expression of SAP in SLE T cells normalized IL-2 production, calcium (Ca2+) responses, and tyrosine phosphorylation of a number of proteins. Exposure of normal T cells to SLE serum IgG, known to contain anti-CD3/TCR Abs, resulted in SAP downregulation. We conclude that SLE T cells display reduced levels of the adaptor protein SAP, probably as a result of continuous T cell activation and degradation by caspase-3. Restoration of SAP levels in SLE T cells corrects the overexcitable lupus T cell phenotype.
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ISSN:0022-1767
1550-6606
1550-6606
DOI:10.4049/jimmunol.1501523