Protein-antigen specific Ia-restricted cytolytic T cells: analysis of frequency, target cell susceptibility, and mechanism of cytolysis.

We previously showed that cloned, antigen-specific, Ia-restricted L3T4a+ T cell lines can be cytolytic for antigen-pulsed B cell lymphoma targets. Such cells can also, under different experimental conditions, activate B cells to proliferate and secrete immunoglobulin. In the present experiments, we show that this functional phenotype is a common one among a panel of cloned T cell lines. In keeping with this finding, freshly isolated, antigen-activated lymph node T cells show similar functional properties. Such cytolytic L3T4a+ T cells differ from classical H-2K/D-restricted cytolytic T cells in two distinct ways. First, Ia-restricted cytolytic T cells can kill bystander targets, whereas H-2K/D-specific cytolytic T cells do not. Second, in testing a panel of target cells by using lectin-mediated cytolysis, Ia-restricted cytolytic clones reveal large differences in target cell susceptibility, whereas all targets are similarly susceptible to H-2K/D-specific killer cells. Finally, evidence is presented that both direct and bystander killing effected by L3T4a+ T cells are mediated by the same soluble factors, in that there is a strong positive correlation of these two activities for individual cloned lines. The relevant mediators appear to be lymphotoxin and IFN-gamma, although the latter molecule by itself is not cytolytic on our target lines.