Human CD81 directly enhances Th1 and Th2 cell activation, but preferentially induces proliferation of Th2 cells upon long-term stimulation

Here it is shown that stimulation of CD81 on human T cells can enhance T cell activation by antigen or superantigen, causing an increase in the early activation marker CD69, and increasing the number of cytokine-producing and proliferating T cells. Interestingly, CD81 costimulates cytokine production by T cells producing both Th1 and Th2 cytokines. Although human CD81 is highly expressed on non-T as well as T cells, CD81 costimulation appears to act directly on T cells. Pre-incubation of purified T cells with anti-CD81 antibody is sufficient to increase T cell activation, while pre-incubation of non-T cells is not. However, long-term polyclonal stimulation of T cells by anti-CD3 antibody, in the presence of CD81 costimulation, biases T cells towards the production of IL-4 and not IFNγ. This is accomplished by a preferential proliferation of IL-4-producing cells.Thus, signalling through CD81 on T cells costimulates both Th1 and Th2 cells, but increases the number of Th2 cells during long-term activation.The tetraspanins are a family of cell-surface proteins with four transmembrane domains, two extracellular loops, and conserved cysteine residues at key positions in the second extracellular loop [1]. They facilitate a wide array of functions, including cell activation, differentiation, adhesion, morphological changes, and motility, which may all relate to the promiscuous associations of these molecules with integrins and other signaling proteins within the cell membrane and the cytoskeleton.CD81, a defining member of the tetraspanin superfamily, is widely expressed on human hematopoietic and other cells [2]. It associates on B cells with a signaling complex that includes CD19 and CD21 [3], as well as associating with MHC class II molecules [4] and other tetraspanins [5,6]. On T cells, CD81 interacts with CD4, CD8, CD82, and selected integrins [7-10].An anti-CD81 antibody was first isolated for its ability to induce cell death in B cell lines [11]. This is likely depen