The signaling lymphocytic activation molecule SLAMF1 (CD150) is a co-stimulatory molecule that is expressed by most immune cells, including T regulatory (Treg) lymphocytes. Since different abnormalities have been reported regarding the number and function of Foxp3+ Treg cells in patients with systemic lupus erythematosus (SLE), we decided to analyze the expression and function of CD150 in these regulatory lymphocytes in this condition. We isolated peripheral blood mononuclear cells from 20 patients with SLE, and 20 healthy controls. The expression of SLAMF1 was determined by multi-parametric flow cytometry and the suppressive function of CD4+CD25+ lymphocytes, upon engagement or not of CD150 with an agonistic monoclonal antibody, was analyzed by an assay of inhibition of cell proliferation. We observed a significantly increased expression of SLAMF1 by CD3+CD4+ helper T cells and CD19+ B cells in patients with SLE and active disease. However, similar levels of SLAMF1 expression were detected in Foxp3+ Treg cells from patients and controls. In contrast, a higher proportion of SLE patients increased their suppressive function of Treg cells upon CD150 engagement compared to healthy controls. Our data suggest that SLAMF1 is another significant piece in the intricate defective immune-regulatory function of patients with SLE.
CannonsJLTangyeSGSchwartzbergPL. SLAM family receptors and SAP adaptors in immunity. Annu Rev Immunol2011; 29: 665–705.
2.
VeilletteA. SLAM family receptors regulate immunity with and without SAP-related adaptors. J Exp Med2004; 199: 1175–1178.
3.
BrowningBMJeVreyEWoodliV. The T cell activation marker CD150 can be used to identify alloantigen-activated CD4+25+ regulatory T cells. Cell Immunol2004; 227: 129–139.
4.
AversaGChangCCCarballidoJMCocksCBVriesJE. Engagement of the signaling lymphocytic activation molecule (SLAM) on activated T cells results in IL-2-independent, cyclosporin A-Sensitive T cell proliferation and IFN-γ production. J Immunol1997; 158: 4036–4044.
5.
HowieDOkamotoSRietdijkS. The role of SAP in murine CD150 (SLAM)-mediated T-cell proliferation and interferon γ production. Blood2002; 100: 2899–2907.
6.
AversaGCarballidoJPunnonenJ. SLAM and its role in T cell activation and Th cell responses. Immunol Cell Biol1997; 75: 202–205.
7.
VeilletteADongZLatourS. Consequence of the SLAM-SAP signaling pathway in innate-like and conventional lymphocytes. J Immunol2007; 27: 698–710.
8.
SchwartzbergPLMuellerKLCannonJL. SLAM receptors and SAP influence lymphocyte interactions, development and function. Nat Rev Immunol2009; 9: 39–46.
9.
MaCSNicholsKETangyeSG. Regulation of cellular and humoral immune responses by the SLAM and SAP families of molecules. Annu Rev Immunol2007; 25: 337–379.
10.
WangNSatoskarAFaubionW. The cell surface receptor SLAM controls T cell and macrophage functions. J Exp Med2003; 199: 1255–1264.
11.
McCauslandMMYusufITranHOnoNYanagiYCrottyS. SAP regulation of follicular helper CD4 T cell development and humoral immunity is independent of SLAM and Fyn kinase. J Immunol2007; 178: 817–828.
12.
BhatREissmannPEndtJHoffmannSWatzlC. Fine-tuning of immune responses by SLAM-related receptors. J Leukoc Biol2006; 79: 417–424.
13.
CocksBGChia-ChunJCarbadilloJMYsselHde VriesYHAversaG. A novel receptor involved in T-cell activation. Nature1995; 376: 260–263.
14.
MinagawaHTanakaKOnoNTatsuoHYanagiY. Induction of the measles virus receptor SLAM (CD150) on monocytes. J Gen Virol2001; 82: 2913–2917.
ShlapatskaLMMikhalapSVBerdovaAG. CD150 association with either the SH2-containing inositol phosphatase or the SH2-containing protein tyrosine phosphatase is regulated by the adaptor protein SH2D1A. J Immunol2001; 166: 5480–5487.
17.
PunnonenJCocksBGCarballidoJM. Soluble and membrane-bound forms of signaling lymphocytic activation molecule (SLAM) induce proliferation and Ig synthesis by activated human B lymphocytes. J Exp Med1997; 185: 993–1004.
18.
BergerSBRomeroXMaC. SLAM is a microbial sensor that regulates bacterial phagosome functions in macrophages. Nat Immunol2010; 11: 920–927.
19.
WangNSatoskarAFaubionW. The cell surface receptor SLAM controls T cell and macrophage functions. J Exp Med2004; 199: 1255–1264.
20.
VeilletteA. Immune regulation by SLAM family receptors and SAP-related adaptors. Nat Rev Immunol2006; 6: 56–66.
21.
SchusterVKrethHW. X-linked lymphoproliferative disease is caused by deficiency of a novel SH2 domain-containing signal transduction adaptor protein. Immunol Rev2000; 178: 21–28.
22.
HagbergNTheorellJSchlumsHElorantaMLBrycesonYTRönnblomL. Systemic lupus erythematosus immune complexes increase the expression of SLAM family members CD319 (CRACC) and CD229 (LY-9) on plasmacytoid dendritic cells and CD319 on CD56(dim) NK cells. J Immunol2013; 191: 2989–2998.
23.
ChatterjeeMRauenTKis-TothK. Increased expression of SLAM receptors SLAMF3 and SLAMF6 in systemic lupus erythematosus T lymphocytes promotes Th17 differentiation. J Immunol2012; 188: 1206–1212.
24.
ChatterjeeMKis-TothKThaiTHTerhorstCTsokosGC. SLAMF6-driven co-stimulation of human peripheral T cells is defective in SLE T cells. Autoimmunity2011; 44: 211–218.
25.
KimJRMathewSOPatelRKPertusiRMMathewPA. Altered expression of signalling lymphocyte activation molecule (SLAM) family receptors CS1 (CD319) and 2B4 (CD244) in patients with systemic lupus erythematosus. Clin Exp Immunol2010; 160: 348–358.
26.
WandstratAENguyenCLimayeN. Association of extensive polymorphisms in the SLAM/CD2 gene cluster with murine lupus. Immunity2004; 21: 769–780.
27.
JørgensenTNAlfaroJEnriquezHL. Development of murine lupus involves the combined genetic contribution of the SLAM and FcγR intervals within the Nba2 autoimmune susceptibility locus. J Immunol2010; 184: 775–786.
28.
ChoubeyD. Interferon-inducible Ifi200-family genes as modifiers of lupus susceptibility. Immunol Lett2012; 147: 10–17.
29.
MoserKLNeasBRSalmonJE. Genome scan of human systemic lupus erythematosus: evidence for linkage on chromosome 1q in African-American pedigrees. Proc Natl Acad Sci USA1998; 95: 14869–14874.
30.
TsaoBPCantorRMKalunianKC. Evidence for linkage of a candidate chromosome 1 region to human systemic lupus erythematosus. J Clin Invest1997; 99: 725–731.
31.
TsaoBPCantorRMGrossmanJM. Linkage and interaction of loci on 1q23 and 16q12 may contribute to susceptibility to systemic lupus erythematosus. Arthritis Rheum2002; 46: 2928–2936.
32.
KomoriHFurukawaHMoriS. A signal adaptor SLAM-associated protein regulates spontaneous autoimmunity and Fas-dependent lymphoproliferation in MRL-Faslpr lupus mice. J Immunol2006; 176: 395–400.
33.
Alvarado-SanchezBHernández-CastroBPortales-PerezD. Regulatory T cells in patients with systemic lupus erythematosus. J Autoimmun2006; 27: 110–118.
34.
Portales-PérezDGonzález-AmaroRAbud-MendozaCSánchez-ArmássS. Abnormalities in CD69 expression, cytosolic pH and Ca2+ during activation of lymphocytes from patients with systemic lupus erythematosus. Lupus1997; 6: 48–56.
