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

• Published in: The 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
• Language: English
• Published: United States 15.06.2016
• Subjects: Adult; Aged; Calcium - metabolism; Caspase 3 - metabolism; Down-Regulation; Female; Humans; Immunoglobulin G - immunology; Interleukin-2 - biosynthesis; Interleukin-2 - immunology; Lupus Erythematosus, Systemic - blood; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - physiopathology; Lymphocyte Activation; Male; Middle Aged; Phosphorylation; Receptors, Antigen, T-Cell - immunology; Signal Transduction; Signaling Lymphocytic Activation Molecule Associated Protein - genetics; Signaling Lymphocytic Activation Molecule Associated Protein - metabolism; Signaling Lymphocytic Activation Molecule Family - genetics; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Tyrosine - metabolism; Young Adult
• ISSN: 0022-1767; 1550-6606; 1550-6606
• DOI: 10.4049/jimmunol.1501523

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.