Identification of alphaCD2 stimulation induced genes in human T-lymphocytes by representational difference analysis

T cells play an important role in the cellular immune response. The signals, however, that are transduced from the cell surface to the nucleus, leading to protein expression and finally to T cell effector function, are still not completely unveiled. Identifying changes in gene expression following T cell activation provides a basis for understanding the molecular events occuring during a T cell response. Signals from both the T cell receptor (TcR) and costimulatory molecules such as CD2 are required to efficiently activate a T cell. CD2 signaling not only enhances TcR induced T cell effector function but plays a unique role in the regulation of T cell anergy and is involved in thymic positive selection suggesting the usage of different signaling pathways for CD2 and the TcR. In the present study, we will use representational difference analysis (RDA) to uncover the genes specifically induced by triggering CD2, which will provide us with a means to interfere at certain stages of cellular activation and thus to modulate the immune response in individuals suffering from hyperreactive immunolocical responses as is the case in autoimmune diseases or transplant rejection.

CD2 is involved in the initial stages of cell contact and facilitates T cell receptor stimulation induced T cell activation. Other functions of CD2 include the inhibition of apoptosis, the regulation of anergy, thymic positive selection, and the T cell response to IL-12. Thus, CD2 stimulation delivers costimulatory signals required for an optimal T cell response. Interfering with this costimulatory pathway (so far performed with anti-CD2 antibodies or an CD58/IgG fusion protein) may provide a means to therapeutically prevent maximal activation of T cells or downregulate already activated T lymphocytes in cases of autoimmune diseases or graft rejection. Thus, the understanding of the molecular events following CD2 mediated T cell stimulation and the knowledge of the genes involved in T cell activation, proliferation, and survival might help to develop new therapeutical approaches in immunosuppressive therapy via interfering with specific T cell effector functions. The detailed gene expression pattern, which is induced following CD2 triggering and which is potentially important for T cell activation/proliferation/survival, however, is still unknown. In our study `Identification of aCD2 stimulation induced genes in human T cells by representational difference analysis` we started to identify genes which are activated in human T cells following stimulation via CD2. In future experiments the expression of these genes will be inhibited using antisense oligonucleotides to analyze the role these genes play in CD2 stimulation specific T cell activation events. Simultaneously, we will investigate to which extent these antisense oligonucleotides influence anti-CD3 e induced T cell activation. This strategy might finally reveal new means to modulate T cell function.