Clonal Induction of Helper T Cells: Conversion of Specific Signals into Nonspecific Signals

The mechanism by which murine helper T cells specific for sheep erythrocytes (SRC) or horse erythrocytes (HRC) exert their effect in an antibody response has been studied in a specific in vitro helper assay in which T cells specific for SRC (T’SRC) do not support an antibody response against HRC and in which T cells specific for HRC (T’HRC) do not support an antibody response against SRC. Either population of helper T cells can support an antibody response to both antigens if the homologous and an unrelated antigen are present at the same time. The helper effect is mediated by stable soluble products, the induction of which is antigen specific and independent of B cells. To exclude T cell-T cell interactions, pure populations of specific helper T cells were obtained by long-term culture in vitro of in vivo primed T cells followed by single cell cloning. Clones of TSRC or T’HRC are highly specific both in vitro and in vivo. For in vivo experiments syngeneic nude mice, selectively and specifically reconstituted with cloned helper T cells, were used. While specific helper T cells can also provide help in vitro for an unrelated antigen, in vivo only specific T cell help is revealed. The results indicate that the specificity of helper T cells is restricted to the interaction of a specific T cell receptor with the antigen which leads to the release of biologically active mediators which themselves have no antigen specificity.