Generation and Cloning of Antigen-Specific Human T-Cells

The ability to grow antigen-spectfic human T-cell clones in vitro has been instrumental in understanding T-cell function. A major breakthrough in T-cell culture in vitro was the discovery of the T-cell growth-inducing properties of interleukin-2 (IL-2), originally called T-cell growth factor or TCGF, by Morgan et al (1 ), who for the first time were able to grow human T-lymphocytes, isolated from human bone marrow. Shortly thereafter, Gillis and Smith (2 ) reported the cloning and long-term culture of mouse cytotoxic T-cells, using TCGF. In spite of the success of growing human T-cells in vitro, the cloning of these cells, however, turned out to be more difficult in contrast to mouse cell lines that could be maintained in culture in the presence of TCGF-containing supernatant only, long-term cultures of cloned human allo-antigen-specific T-cell lines (3 , 4 ) needed repetitive stimulation with specific allo-antigen for then growth (3 ) This led to the general assumption that antigen-specific IL-2-dependent T-cell lines and T-cell clones would lose then antigen responsiveness when propagated with IL-2 in the absence of specific antigen.