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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD / immunology*
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Antigens, CD / metabolism
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CD28 Antigens / immunology
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CD3 Complex / immunology
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Cytokines / metabolism
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Humans
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Lupus Erythematosus, Systemic / immunology*
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Lupus Erythematosus, Systemic / metabolism
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Lymphocyte Activation / immunology*
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NF-kappa B / genetics
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NF-kappa B / metabolism
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Receptors, Cell Surface / immunology*
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Receptors, Cell Surface / metabolism
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Signal Transduction / immunology
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Signaling Lymphocytic Activation Molecule Family
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Signaling Lymphocytic Activation Molecule Family Member 1
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
Substances
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Antigens, CD
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CD28 Antigens
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CD3 Complex
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Cytokines
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NF-kappa B
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Receptors, Cell Surface
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SLAMF6 protein, human
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Signaling Lymphocytic Activation Molecule Family
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Signaling Lymphocytic Activation Molecule Family Member 1