Human T lymphocytes stimulated by phytohaemagglutinin undergo a single round of cell division without a requirement for interleukin-2 or accessory cells.

Monocyte-depleted human T lymphocytes completed a single round of DNA synthesis and cell division when treated with phytohaemagglutinin (PHA). Direct assay of culture supernatants showed that very low amounts of interleukin-2 (IL-2) were synthesized in these cultures. Furthermore, the first round of cell division was totally unaffected by the addition of saturating amounts of anti-Tac, a monoclonal antibody against the IL-2 receptor. These data strongly suggest that stimulation of IL-2 receptors by IL-2 was not required for the completion of the first round of mitosis. By contrast, proliferation of the daughter cells produced by the first cell doubling required the addition of exogenous IL-2 and was totally abolished by anti-Tac. These results were confirmed by experiments using single lymphocytes, which also showed that accessory cells were not required during the first cell doubling of PHA-stimulated lymphocytes. We therefore propose a modified model for in vitro T-lymphocyte activation, wherein PHA stimulate a single round of cell proliferation without a requirement for stimulation by IL-2. The resulting daughter cells now require IL-2 for further proliferation. By analogy, we suggest that triggering by antigen in vivo (in the context of products of the major histocompatibility locus) may also stimulate a single round of IL-2-independent division in appropriate clones of T lymphocytes, with the resulting population of daughter cells requiring IL-2 for further expansion of the population.