710 Helper T Cells in the Generation

Although cooperative interactions between helper T cells and B-cell precursors have been extensively characterized (1, 2), the role of helper T cells in the triggering and differentiation of cytotexic T-cell precursors remains ambiguous. Several laboratories have described synergistic interactions between T cells recognizing H-2K or D antigens (SD) and T cells recognizing Ia antigens (LD); increased anti-H-2-directed cytotoxicity is generated if both H-2K or D and Ia antigens are foreign to the responding T cell (3-5). This suggests that cooperation between anti-Ia helpers and anti-H-2 killer precursors augments cytotoxicity. However, this type of cooperation must not be essential since Forman and Klein, and Klein et al., have shown that cytotoxicity is generated when the only antigenic difference between responder T cells and stimulator cells is derived from a mutation in the H-2D or H-2K end of the histocompatibility gene complex (i.e., there is no detectable Ia antigenic difference between the stimulator and responder cells) (6, 7). A different type of cooperative interaction in the induction of cytotoxic T-cell precursors has been observed by both Cohen and Howe (8) and by Wagner (9). In these experiments, lymph node responder cells were co-cultured with syngeneic thymocytes as well as allogeneic stimulator cells. A cytotoxic response was obtained from low doses of lymph node cells co-cultured with thymocytes and stimulator cells, although neither cell population responded well alone. Unfortunately, these experiments did not allow a clearcut definition of the helper effect since the cytotoxic cells produced were derived from both lymph node and thymocyte populations (9) and the antigen specificity of the interaction was not investigated. More recently, Plate has described a soluble factor which augments the cytotoxicity generated by a helper T-cell-depleted culture, but again the specificity of the interaction was not investigated and the helper factor was not an essential requirement for the generation of cytotoxicity (10).