A novel receptor involved in T-cell activation

Abstract

OPTIMAL T-cell activation and T-cell expansion require triggering by T-cell antigen receptors and co-stimulatory signals provided by accessory cells^1á¤-3. A major co-stimulatory pathway involves crosslinking the CD28 molecule on T cells by its ligands CD80 or CD86 expressed on antigen-presenting cells^4á¤-7. But recent studies^8,9 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 (Mr 70K), designated SLAM, that belongs to the immunoglobulin gene superfamily, which is involved in T-cell stimulation. SLAM is constitutively expressed on peripheral-blood CD45RO^high 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-γ (IFN-γ) is strongly upregulated, even in T helper type 2 (Th2) CD4⁺ T-cell clones, whereas no induction of inter leu kin(lL)-4 or IL-5 production was observed in Thl 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 ThO/Thl cytokine production profile.