The human LT system. XI. Identification of LT and "TNF-like" forms from stimulated natural killers, specific and nonspecific cytotoxic human T cells in vitro.

These studies demonstrate that specific and nonspecific cytolytic human T cells can release LT forms in vitro. Nonspecific cytolytic T cells were derived from IL 2-dependent cultures initiated by allogeneic mixed lymphocyte reaction (AMLR). Specific cytolytic T cells (CTL) were derived from IL 2-dependent T cell clones, initiated by mixed lymphocyte reaction and specific for class II antigens. alpha-LT was the major lytic component released by these cells in IL 2-dependent cultures. However, on Con A stimulation or contact with target cells, both AMLR and CTL effectors release a new LT form. The new LT form released by AMLR and CTL effectors appear similar, for they both elute from gel filtration at 60,000 to 70,000 m.w. and migrate as a single peak with an Rf of 0.4 on 7% native PAGE tube gels. Moreover, testing these materials on a panel of target cells in vitro indicates that they are both nonspecific, and lyses NK-resistant target cells in vitro. Additional studies revealed that in vitro lytic activity of this form(s) is not affected by either anti-alpha-LT serum or a monoclonal reagent which inactivates macrophage cell toxins (MCT) and tumor necrosis factor (TNF). However, when these two immunologic reagents are tested together, activity is totally neutralized. Thus, this LT form expresses antigens in common with alpha-LT, MCT, and TNF. Finally, studies with NK-CF and NK-LT forms revealed that they were also completely neutralized with a mixture of anti-LT and monoclonal anti-TNF antibody. These data suggest that certain macrophage- and lymphocyte-derived cell toxins are interrelated.