Engagement of the signaling lymphocytic activation molecule (SLAM) on activated T cells results in IL-2-independent, cyclosporin A-sensitive T cell proliferation and IFN-gamma production.
The expression and function of the novel signaling lymphocytic activation molecule (SLAM) are described. SLAM is present on immature thymocytes, CD45R0(high) memory T cells, T cell clones, CD56+ T cells, EBV-transformed B-cell lines and on a proportion of B cells. SLAM is rapidly induced on naive T cells, TCR gammadelta+ T cells, and B cells following activation. Engagement of SLAM by the agonistic anti-SLAM mAb A12 resulted in proliferation of T cell clones and Ag- or PHA-activated peripheral blood T cells. mAb A12-induced T cell proliferation is independent of IL-2 and sensitive to inhibition by cyclosporin A. The extent of the anti-SLAM-induced proliferation was related to the activation state of the T cells, since fully rested T cell clones failed to proliferate in response to mAb A12 stimulation, despite unchanged SLAM expression on their surface. Ligation of SLAM on activated peripheral T cells or T cell clones by mAb A12 induced IFN-gamma production in the absence of other exogenous stimuli, even in allergen-specific Th2 clones. These data indicate that stimulation via SLAM reverses the cytokine production profile of Th2 clones to a Th0 phenotype, whereas it further polarizes cytokine production by Th1 clones. Thus, SLAM is a novel receptor that mediates IL-2-independent expansion of activated T cells during immune responses, while concomitantly directing these proliferating cells to a Th0/Th1 pathway.
Aversa
G
G
DNAX Research Institute of Molecular and Cellular Biology, Human Immunology Department, Palo Alto, CA 94304, USA.
Chang
C C
CC
Carballido
J M
JM
Cocks
B G
BG
de Vries
J E
JE
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016572:Cyclosporine / Q000494:pharmacology; D005434:Flow Cytometry; D015870:Gene Expression; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D007136:Immunoglobulins / Q000502:physiology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000502:physiology; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000276:immunology*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D006023:Glycoproteins; D007136:Immunoglobulins; D007376:Interleukin-2; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D007371:Interferon-gamma; D016572:Cyclosporine