Increased expression of SLAM receptors SLAMF3 and SLAMF6 in systemic lupus erythematosus T lymphocytes promotes Th17 differentiation.

Chatterjee M1, Rauen T, Kis-Toth K, Kyttaris VC, Hedrich CM, Terhorst C, Tsokos GC.
Source: J Immunol
Publication Date: (2012)
Issue: 188(3): 1206-12
Research Area:
Cancer Research/Cell Biology
Immunotherapy / Hematology
Gene Expression
Basic Research
Culture Media:

Primary total T cells were isolated from peripheral venous blood by negative selection and kept in RPMI 1640 medium supplemented with 10% FBS. Naive (CD4+ CD45RA+) and memory (CD4+ CD45RO+ ) T cells were purified using T cell isolation kits from Miltenyi Biotec according to the manufacturer’s instructions.

Naive and memory CD4+ T cells (1 3 106 /well) were differentiated into Th17 cells in serum-free X-VIVO 10 medium (BioWhittaker) by the addition of IL-6 (25 ng/ml), TGF-b1 (5 ng/ml), IL-1b (12.5 ng/ml), IL-21 (25 ng/ml), and IL-23 (25 ng/ml) for up to 7 days.


Altered T cell function in systemic lupus erythematosus (SLE) is determined by various molecular and cellular abnormalities, including increased IL-17 production. Recent evidence suggests a crucial role for signaling lymphocyte activation molecules (SLAMs) in the expression of autoimmunity. In this study, we demonstrate that SLAMF3 and SLAMF6 expression is increased on the surface of SLE T cells compared with normal cells. SLAM coengagement with CD3 under Th17 polarizing conditions results in increased IL-17 production. SLAMF3 and SLAMF6 T cell surface expression and IL-17 levels significantly correlate with disease activity in SLE patients. Both naive and memory CD4(+) T cells produce more IL-17 in response to SLAM costimulation as compared with CD28 costimulation. In naive CD4(+) cells, IL-17 production after CD28 costimulation peaks on day 3, whereas costimulation with anti-SLAMF3 and anti-SLAMF6 Abs results in a prolonged and yet increasing production during 6 d. Unlike costimulation with anti-CD28, SLAM costimulation requires the presence of the adaptor molecule SLAM-associated protein. Thus, engagement of SLAMF3 and SLAMF6 along with Ag-mediated CD3/TCR stimulation represents an important source of IL-17 production, and disruption of this interaction with decoy receptors or blocking Abs should mitigate disease expression in SLE and other autoimmune conditions.