Abstract
Signaling lymphocyte activation molecule (SLAM), a glycoprotein expressed on activated lymphocytes and antigen-presenting cells, has been shown to be a coregulator of antigen-driven T cell responses and is one of the two receptors for measles virus. Here we show that T cell receptor-induced interleukin (IL)-4 secretion by SLAM(-/-) CD4(+) cells is down-regulated, whereas interferon gamma production by CD4(+) T cells is only slightly up-regulated. Although SLAM controls production of IL-12, tumor necrosis factor, and nitric oxide in response to lipopolysaccharide (LPS) by macrophages, SLAM does not regulate phagocytosis and responses to peptidoglycan or CpG. Thus, SLAM acts as a coreceptor that regulates signals transduced by the major LPS receptor Toll-like receptor 4 on the surface of mouse macrophages. A defective macrophage function resulted in an inability of SLAM(-/-) C57Bl/6 mice to remove the parasite Leishmania major. We conclude that the coreceptor SLAM plays a central role at the interface of acquired and innate immune responses.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, CD
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Base Sequence
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CD4-Positive T-Lymphocytes / immunology
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DNA Primers
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Glycoproteins / genetics
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Glycoproteins / immunology*
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Immunoglobulins / genetics
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Immunoglobulins / immunology*
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Leishmania major / immunology
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Leishmaniasis, Cutaneous / immunology
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Lipopolysaccharides / immunology
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Macrophages, Peritoneal / immunology*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Mutant Strains
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / immunology*
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Receptors, Antigen, T-Cell, alpha-beta / immunology
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Receptors, Cell Surface
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Recombinant Proteins / immunology
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Reverse Transcriptase Polymerase Chain Reaction
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Signaling Lymphocytic Activation Molecule Family Member 1
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T-Lymphocytes / immunology*
Substances
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Antigens, CD
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DNA Primers
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Glycoproteins
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Immunoglobulins
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Lipopolysaccharides
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Receptors, Antigen, T-Cell
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Receptors, Antigen, T-Cell, alpha-beta
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Receptors, Cell Surface
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Recombinant Proteins
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Signaling Lymphocytic Activation Molecule Family Member 1