The cell surface receptor SLAM controls T cell and macrophage functions.
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.
Wang
Ninghai
N
Division of Immunology, RE-204, Beth Israel Deaconess Medical Center, Harvard Medical School, 41 Avenue Louis Pasteur, Boston, MA 02215, USA.
Satoskar
Abhay
A
Faubion
William
W
Howie
Duncan
D
Okamoto
Susumu
S
Feske
Stefan
S
Gullo
Charles
C
Clarke
Kareem
K
Sosa
Miriam Rodriguez
MR
Sharpe
Arlene H
AH
Terhorst
Cox
C
D000818:Animals; D015703:Antigens, CD; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D017931:DNA Primers; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology*; D018320:Leishmania major / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D017931:DNA Primers; D006023:Glycoproteins; D007136:Immunoglobulins; D008070:Lipopolysaccharides; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1