The induction of lymphocytes with the capacity to render macrophages cytotoxic in an allogeneic murine system.

Sensitized spleen and peripheral lymph node lymphocytes were tested after different types of immunization with allogeneic tumour cells for their capacity to induce macrophage cytotoxicity in vitro. The macrophages were rendered cytotoxic either by direct contact with lymphocytes and tumour cells (activation of macrophages) or by a factor (macrophage arming factor, MAF), released by the sensitized lymphocytes incubated with tumour cells (arming of macrophages). Both types of reactions are T-cell dependent. Macrophage activation is a more sensitive way to detect lymphocytes with the capacity to render macrophages cytotoxic than arming of macrophages. The route of immunization subcutaneously (s.c.) or intraperitoneally (i.p.) with allogeneic cells did not influence the induction of lymphocytes with the capacity to render macrophages cytotoxic. However, the tumour cells had to be intact as disrupted cells (suspended in Freund's complete adjuvant, FCA) did not induce macrophages activating lymphocytes. The adjuvant dimethyl dioctadecyl ammonium bromide (DDA) did not increase the lymphocyte response. Intact allogeneic tumour cells were needed in vitro when used for secondary antigenic stimulation. This secondary stimulation was independent of antigen presentation by macrophages. This suggests that also in vivo the primary response is independent of macrophage antigen presentation. Delayed-type hypersensitivity and antibody responses against the allogeneic tumour cells were comparable after s.c. and i.p. immunization and after immunization with FCA and DDA.