Mitogenic effect of interleukin-2 on unstimulated human T cells: an editorial review

The most salient feature of the lymphokine interleukin-2 (IL-2), a hormone-like protein, is its ability to sustain the proliferation of immunocompetent T cells. Results of initial studies characterizing IL-2 in vitro led investigators to conclude that IL-2 had no known effects on lymphocytes that had not been previously activated by exposure to a mitogen or antigen. Several groups postulated that T cell growth required two signals. The first signal, delivered by a mitogen or antigen, induced T cell activation. Resting T cells, which were thought to lack the membrane receptor for interleukin-2 (IL-2R), progressed from the G0-G1 phase to the S phase, during which time they converted from IL-2R- to IL-2R+ cells. Thereafter, the second signal, served by IL-2, induced T cell proliferation of the IL-2R+ cells. Recently, a number of investigators have demonstrated that highly purified preparations of both natural and recombinant IL-2 induced high levels of T cell proliferation in the absence of any known mitogens or antigens. Presented herein is a review of these studies and an overview of the hypotheses of the mechanisms whereby IL-2 alone induces T cell activation and proliferation.