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Lymph node and spleen cells from normal mice were cultured for 3 days with polyoma virus-induced tumour, Ehrlich's ascites turnout or leukaemia L 1210 cells. This resulted in in vitro immunization of the lymphocytes, which were then transferred to irradiated target cells labelled with 51Cr. Normal, i.e. non-immune thioglycollate-stimulated peritoneal macrophages were also added to some tubes. Non-immune macrophages mixed with immunized lymphocytes showed a significantly increased ability to destroy tumour ceils as compared with macrophages in the absence of immunized lymphocytes. The immunized lymphocytes were almost entirely inactive alone. When the number of macrophages was kept constant the cytotoxicity was dependent on the number of viable immunized lymphocytes placed on the target cells. Immunized lymphocytes, in the presence of macrophages, only exhibited strong killing of the target cells against which they had been immunized; some lysis of ‘bystander’ cells was, however, seen provided specific target cells were present. Macrophage monolayers exposed to immunized lymphocytes upon contact with specific antigen became ‘armed’ and showed a significant cytotoxicity for specific target cells. When immunized lymphocytes and normal macrophages were treated with actinomycin D and puromycin, cytotoxicity was inhibited in the immunized lymphocytes but not in the macrophages. The possible mechanism of normal macrophage cooperation with immunized lymphocytes in the cytotoxic killing reaction is discussed. Results presented in this paper favour the view that immunologically specific cytophilic factor (presumptive cytophilic antibody) is involved in the macrophage-mediated cytotoxicity in the system studied. [ABSTRACT FROM AUTHOR]

In a previous paper it had been shown that up to 40% of human peripheral lymphocytes will make rosettes with sheep red cells. In this study the inhibitory effect of antilymphocyte serum (ALS) and of certain other preparations on this rosette phenomenon is described. ALS was prepared in horses by injection of human peripheral lymphocytes and rosette-inhibiting, cytotoxic and agglutinating titres were determined during immunization. The ALS had been tested in vivo by regional administration to vervet monkeys bearing skin allografts. It was found t h a t the peak of rosette-inhibiting titre appeared to provide a good index of immunosuppressive activity. These peaks, and the accompanying periods of immunosuppressive activity, were of short duration, in contrast to the levels of cytotoxic and agglutinathig titres. Antihuman lymphocyte sera had considerable rosette-inhibiting titres against the lymphocytes of the baboon (Papio papio) but little against those of the vervet monkey (Cercopithecus aethiops). Inhibition by ALS of the phenomenon described by us is unaffected by complement. Antihuman globulin serum and phytohaemagglutinin had no inhibitory effect. Digestion of ALS with pepsin to obtain the F (ab')2 fragment had only a slight effect on rosette-inhibiting titres, while it reduced the cytotoxic activity very considerably. The phenomenon described by us is probably different from that reported by other workers, in which only a small proportion of lymphocytes form rosettes. [ABSTRACT FROM AUTHOR]