A novel receptor involved in T-cell activation.
Optimal T-cell activation and T-cell expansion require triggering by T-cell antigen receptors and co-stimulatory signals provided by accessory cells. A major co-stimulatory pathway involves crosslinking the CD28 molecule on T cells by its ligands CD80 or CD86 expressed on antigen-presenting cells. But recent studies on CD28-deficient mice have indicated that CD28 is not required for all T-cell responses and that additional T-cell co-stimulatory pathways exist. Here we describe a novel glycoprotein, of relative molecular mass 70,000 (M(r) 70K), designated SLAM, that belongs to the immunoglobulin gene superfamily, which is involved in T-cell stimulation. SLAM is constitutively expressed on peripheral-blood CD45ROhigh memory T cells, T-cell clones, immature thymocytes, and a proportion of B cells, and is rapidly induced on naive T cells after activation. Engagement of SLAM enhances antigen-specific proliferation and cytokine production by T cells carrying the CD4 antigen (CD4+). Particularly, the production of interferon-gamma (IFN-gamma) is strongly upregulated, even in T helper type 2 (Th2) CD4+ T-cell clones, whereas no induction of interleukin (IL)-4 or IL-5 production was observed in Th1 clones. In addition, the engagement of SLAM induces directly the proliferation of CD4+ T-cell clones and preactivated T cells, in the absence of any other stimuli, and without CD28 involvement. Thus SLAM is a novel receptor on T cells that, when engaged, potentiates T-cell expansion in a CD28-independent manner and induces a Th0/Th1 cytokine production profile.
Cocks
B G
BG
DNAX Research Institute of Molecular and Cellular Biology, Human Immunology Department, Palo Alto, California 94304-1104, USA.
Chang
C C
CC
Carballido
J M
JM
Yssel
H
H
de Vries
J E
JE
Aversa
G
G
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D016207:Cytokines / Q000096:biosynthesis; D017931:DNA Primers; D004926:Escherichia coli; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011956:Receptors, Cell Surface; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D016207:Cytokines; D017931:DNA Primers; D006023:Glycoproteins; D007136:Immunoglobulins; D011948:Receptors, Antigen, T-Cell; D011956:Receptors, Cell Surface; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens