SLAMF6-driven co-stimulation of human peripheral T cells is defective in SLE T cells - PubMed (original) (raw)

SLAMF6-driven co-stimulation of human peripheral T cells is defective in SLE T cells

Madhumouli Chatterjee et al. Autoimmunity. 2011 May.

Abstract

The CD28 co-stimulatory pathway is well established for T cell activation. However, there is evidence suggesting the existence of additional co-stimulatory pathways. Here we report that a member of the SLAM superfamily, SLAMF6, or CD352 plays an important role in T cell co-stimulation. Cross-linking of SLAMF6 with anti-CD3 primes human T cell to secrete Th1 cytokines. Among the T cell subsets, CD8(+) and CD3(+)CD4(-)CD8(-) cells display the highest Th1 production responses. Engagement of SLAMF6 mobilizes the modulation of the same set of NF-κB-associated genes. Although the expression of SLAMF6 on the surface of T cells from patients with systemic lupus erythematosus (SLE) T cells is comparable to that on the normal T cells, engagement of SLAMF6 results in severely reduced Th1 and IL-2 cytokine production. Our results suggest the existence of an additional co-stimulatory pathway in human T cells, which is defective in SLE T cells.

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Conflict of interest statement

Declaration of interest: The authors report no conflicts of interest.

Figures

Figure 1

Figure 1

Cell-surface expression of SLAMF6 is upregulated in activated human T cells. Expression was detected on resting and activated T cells by flow cytometry using a PE-labeled monoclonal antibody against SLAMF6. SLAMF6 expression on (A) CD4+, (B) CD8+ and (C) DN T cells.

Figure 2

Figure 2

SLAMF6 co-stimulation leads to production of Th1 cytokines and IL-2 by total T cells. SLAMF6 co-stimulation induces the intracellular production of IFN-γ and TNF-α in (A) CD4+, (B) CD8+ and (C) DN T cells. (D) SLAMF6 co-stimulation leads to IFN-γ and TNF-α secretion by total T cells. Black graphs: IFN-γ; striped graphs: TNF-α. (E) SLAMF6 co-stimulation leads to IL-2 secretion by total T cells.

Figure 3

Figure 3

Cytokine production after SLAMF6 co-stimulation of SLE T cells. SLAMF6 co-stimulation induces the intracellular production of IFN-γ and TNF-α in (A) CD4+, (B) CD8+ and (C) DNSLE T cells. (D) SLAMF6 co-stimulation leads to IFN-γ and TNF-α secretion by total SLE T cells. Black graphs: IFN-γ; striped graphs: TNF-α. (E) SLAMF6 co-stimulation leads to IL-2 secretion by total SLE T cells.

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