METHODS AND COMPISITIONS FOR ACTIVATION HUMAN T CELLS IN VITRO

摘要

4-1BB is a costimulatory member of the TNFR family expressed on activated T cells. Its ligand, 4-1BBL, is expressed on activated antigen presenting cells (APC). Relatively little has been done to study the function of 4-1BB on human T cells. Transfection of the h4-1BBL gene into the murine mastocytoma P815, which can also bind anti-CD3 mAb (OKT3) through its Fc receptor and thus deliver both TCR and costimulatory signals to human T cells, was carried out to assess the function of 4-1BBL in human T cell activation. Human 4-1BBL was shown to expand CD4 and CD8 T cells and is most effective when both CD4 and CD8 T cells are present in the same culture. In addition, and surprisingly, 4-1BBL and co-stimulus was shown to be effective in activating CD28 cells. Furthermore, this co-stimulation was shown to allow upregulation of the T cell survival pathway through Bcl-XL in a CD28 independent fashion. In addition, the invention relates to an additional means of eliciting anti-antigen immunity comprising activation of a T cell using 4-1BBL and the presentation of an antigen or part thereof against which the immunity is desired.