THF, a thymic hormone, promotes interleukin-2 production in intact and thymus-deprived mice

T cells stimulated by mitogen or antigen produce a T cell mediator, interleukin-2 (IL-2), which induces clonal expansion of activated target cells. The activity of IL-2 obtained from cell-free supernatants of spleen cells after 24-h incubation with concanavalin A was tested in an IL-2-dependent blast cell proliferation assay. IL-2 production was found to be diminished in neonatally thymectomized (NTx) mice. Treatment of NTx mice with a series of 14 daily injections of thymic hormone, THF (5-10 ng), resulted in reconstitution of IL-2 activity to the level found in intact, untreated mice. The rise in IL-2 activity was observed to be part of a general reconstitution of the immune capacity in the THF-treated NTx mice, manifested by elevated responses to mitogenic stimulation by T lectins and elevated mixed lymphocyte reactivity and cell-mediated cytotoxicity. Elevation of IL-2 activity could also be detected in vitro when spleen cells from intact mice were preincubated with THF for 24 h. THF did not enhance the production of interleukin-1 (IL-1) by bone marrow-derived macrophages, and in experiments in which T cells and macrophages were separately exposed to THF, augmentation of IL-2 activity was found only when the T cell-enriched spleen fraction was pretreated with THF. This was taken as proof that THF acted exclusively on T cells capable of producing IL-2, and that neither macrophages nor IL-1 were involved in the T helper activity induced by THF. Although THF could induce and/or augment IL-2 production by helper T cells, THF lacked IL-1 and IL-2 characteristics, since it could not maintain IL-2-dependent clonal expansion of target blasts nor induce IL-2 production by activated T cells.