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

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.

Keywords::

• SLAMF6
• co-stimulation
• systemic lupus erythematosus
• Th1
• NF-κB

Declaration of interest: This work was supported by the National Institutes of Health grants [PO1AI065687, RO1AI42269]; and the Kirkland Scholar Program. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.